Gram negative

Am Ind Hyg Assoc J, 1987 Aug, 48(8), 745 - 51
A study of the relationship between airborne contaminants and environmental factors in Dutch swine confinement buildings; Attwood P et al.; A total of 171 swine confinement buildings were studied to determine the concentrations of airborne total and D50 less than or equal to micron 8.5 dust fractions, total and gram-negative bacteria, bacterial endotoxin and NH3 . The concentrations of these airborne contaminants then were correlated statistically to a number of environmental factors such as feeding practices, number of animals and ventilation parameters . The results showed that airborne dust, endotoxin, bacteria and NH3 are commonly in high concentrations within the swine confinement buildings and that these are at levels where health effects have been observed in other studies . Correlation of these airborne contaminants to a number of environmental factors showed that while ventilation is an important criteria for airborne contaminants, there are a number of farming practices that significantly contribute to the levels of airborne contaminants currently found . Pearson correlations indicate a number of important criteria that the industrial hygienist should measure when faced with problems in agricultural confinement buildings.

Forensic Sci Int, 1987 Aug, 34(4), 255 - 6
Death caused by DF-2, following a dog-bite; Theilade P et al.; The Gram-negative rod DF-2 was isolated from blood-cultures, the blood sample taken 3 days after death from a 65-year-old woman who had been bitten in her finger by her dog . At the medico-legal external examination marbling of the skin was found, suggesting septicemia . In persons found dead with a history of dog exposition and with no other obvious cause of death, examination for DF-2 should be performed.

J Bacteriol, 1987 Aug, 169(8), 3654 - 63
Nephelometric determination of turgor pressure in growing gram-negative bacteria; Koch AL et al.; Gas vesicles were used as probes to measure turgor pressure in Ancylobacter aquaticus . The externally applied pressure required to collapse the vesicles in turgid cells was compared with that in cells whose turgor had been partially or totally removed by adding an impermeable solute to the external medium . Since gram-negative bacteria do not have rigid cell walls, plasmolysis is not expected to occur in the same way as it does in the cells of higher plants . Bacterial cells shrink considerably before plasmolysis occurs in hyperosmotic media . The increase in pressure required to collapse 50% of the vesicles as external osmotic pressure increases is less than predicted from the degree of osmotically inducible shrinkage seen with this organism or with another gram-negative bacterium . This feature complicates the calculation of the turgor pressure as the difference between the collapse pressure of vesicles with and without sucrose present in the medium . We propose a new model of the relationship between turgor pressure and the cell wall stress in gram-negative bacteria based on the behavior of an ideal elastic container when the pressure differential across its surface is decreased . We developed a new curve-fitting technique for evaluating bacterial turgor pressure measurements.

Plast Reconstr Surg, 1987 Aug, 80(2), 213 - 25
Craniofacial infection in 10 years of transcranial surgery; David DJ et al.; Infection following transcranial surgery may be devastating . A review of 170 transcranial operations is presented with a focus on postoperative infection and its relationship to patient age, preoperative microbiology, pattern of operation, length of operation, and the use of antibiotic prophylaxis . The overall postoperative infection rate was 6.5 percent, but the infection rate in adults (23.5 percent) was much higher than in children (2.2 percent) . Higher infection rates were found in adults with craniofacial dysostoses undergoing lengthy frontofacial advancements which required tracheostomy airway management . The residual frontal extradural dead space following advancement in adults is a sanctuary to infecting organisms from the respiratory tract--especially Pseudomonas transferred from the tracheostomy site into the upper airway and intracranial dead space by ventilation forces . Operating times for patients who became infected were 2 1/2 hours longer than average operating times for transcranial operations . Preoperative microbiology of the craniofacial region was not a good predictor of subsequent infection . Recommendations include operative intervention at an early age, short preoperative hospital stay, antibiotic prophylaxis to include gram-negative cover, surgical measures to either fill or isolate the dead space, and strict tracheostomy care--preferably with the patient being barrier-nursed.

Eur J Clin Microbiol, 1987 Aug, 6(4), 456 - 9
Emergence of resistance in gram-negative bacteria during therapy with expanded-spectrum cephalosporins; Dworzack DL et al.; To assess the clinical importance of emergence of beta-lactam resistance caused by stable derepression of chromosomal beta-lactamases, sequential cultures from patients treated with expanded-spectrum cephalosporins were monitored for the persistence of bacteria possessing these enzymes . Antibiotic susceptibilities and beta-lactamase production before and after cefoxitin induction were determined in sequential isolates of individual bacterial strains . Of 49 strains isolated from 44 patients, 25 strains (51%) were eradicated by cephalosporin therapy, 17 strains (35%) persisted with unchanged susceptibility in sequential cultures, and 7 strains (14%) from 7 patients developed multiple beta-lactam resistance during cephalosporin therapy . In 6 of the 7 strains, resistance was associated with stable derepression of beta-lactamases . In the patient group whose strains developed resistance, subsequent use of non-beta-lactam antibiotics was more frequent and mortality was higher.

Immunology, 1987 Aug, 61(4), 527 - 33
Characterization of an antigen secreted by Chlamydia-infected cell culture; Stuart ES et al.; A soluble genus-specific chlamydial antigen has been isolated from the supernatants of cultures infected with Chlamydia trachomatis and from other sources . The antigen is a glycolipid that is secreted during the infective cycle . This exoglycolipid can be hydrolysed and fractionated into polysaccharide and lipid components . Both fractions retain antigenic activity . An immunodominant antigenic determinant of the lipid component contains fatty acids of C17 and C18:1 . The polysaccharide immunodominant epitope gives rise to gulose when derivatives are formed . The secretion of the antigen into the media supernatant, the presence of gulose and the observed molecular weight are consistent with properties of alginate secreted by Gram-negative bacteria . Chemical analyses and SDS-PAGE indicate that the exoglycolipid is markedly different from LPS.

J Clin Pharm Ther, 1987 Aug, 12(4), 249 - 54
A comparison of two incubation temperatures for the isolation of gram-negative contaminants from raw materials and non-sterile pharmaceuticals; Ferguson A et al.; Selective and non-selective broth enrichment techniques may be used in the isolation of microbial contaminants from pharmaceutical products . A non-selective method may give better recovery rates for damaged organisms . A trial was carried out to determine whether the recovery of Gram-negative contaminants could be improved by using an incubation temperature of 30 degrees C for 48 h, rather than the more widely used 37 degrees C for 24 h . Contaminants were isolated from 3.2% of samples incubated at the lower temperature compared with 0.8% at the higher temperature . The recovery rate from raw materials improved noticeably (9.0% compared with 0.9%).

Anal Biochem, 1987 Aug 1, 164(2), 320 - 30
A highly efficient procedure for the quantitative formation of intact and viable lysozyme spheroplasts from Escherichia coli; Marvin HJ et al.; This paper describes a highly efficient procedure for the quantitative conversion of Escherichia coli cells to spheroplasts utilizing 100- to 1000-fold less lysozyme than in the most efficient procedures used to date . The resulting spheroplasts have intact outer and inner membranes and are fully viable on agar plates . The spheroplasting procedure is a refinement of earlier procedures and enables regulation of the translocation of minute amounts of lysozyme into the periplasmic space of E . coli cells, based on a Ca2+ pretreatment, an EDTA incubation, and a heat shock . About 1000 lysozyme molecules per cell are sufficient for complete spheroplast formation (greater than 98%) . Some of the characteristics of these spheroplasts prior to and after recovery are described . It is anticipated that such viable spheroplasts will be useful in the study of fusion of gram-negative cells and other membrane systems, in the introduction of DNA and proteins into refractory gram-negative cells, and in investigating envelope-related synthesis and assembly processes.

Am J Physiol, 1987 Aug, 253(2 Pt 1), E123 - 9
Altered glucose kinetics in diabetic rats during gram-negative infection; Lang CH et al.; The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes . Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin . The higher dose produced "severe" diabetes, whereas the lower dose of streptozotocin produced a milder, "latent" diabetes . After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli . After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group . This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration . Glucose turnover, assessed by the constant intravenous infusion of {6-3H}- and {U-14C}glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics . Induction of sepsis produced a slight decrease in the glucose turnover in the severe diabetic group but did not alter turnover in the latent diabetics . The rate of glucose disappearance, used to quantitate the alterations in plasma glucose after an intravenous glucose tolerance test, was decreased in both groups of diabetics and was proportional to the severity of the diabetic state . Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals . Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer, 1987 Jul 15, 60(2), 255 - 62
Imipenem/cilastatin therapy of infections in cancer patients; Bodey GP et al.; Imipenem/cilastatin was administered during 153 febrile episodes occurring in cancer patients and the response rate was 68% . Considering only documented infections the response rate was 71% . Patients who received imipenem as initial therapy had a higher response rate than patients who received it after failing other antibiotics (77% versus 68%) . The overall response rates for septicemias and pneumonias were 75% and 58% . Among the 57 gram-negative infections 77% responded, but the response rate was substantially higher if imipenem was used as initial therapy (94% versus 69%) . The poorest response rate was observed when imipenem was given as secondary therapy for Pseudomonas infections (50%), but most of these patients had failed to respond to other appropriate antibiotics . The only serious side effect was seizures which occurred in ten patients, although eight of them had other predisposing factors . Imipenem appears to be a useful antibiotic for treatment of infections, even in neutropenic cancer patients.

Appl Environ Microbiol, 1987 Jul, 53(7), 1718 - 20
A rapid test for chitinase activity that uses 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide; O'Brien M et al.; A total of 101 strains of bacteria from environmental and clinical sources, most of which were gram negative, were tested for chitobiase activity by using a filter paper spot test with 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide as the substrate . The results were compared with those obtained by a conventional plate method for chitinase activity by using colloidal chitin as the substrate . There was excellent agreement in the results for both methods . The filter paper spot test with 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide has the advantages of being rapid, simple to perform, and inexpensive . This method should be adaptable to a wider range of microorganisms, particularly those with unusual growth requirements.

Appl Environ Microbiol, 1987 Jul, 53(7), 1685 - 9
Bacterial detoxification of diisopropyl fluorophosphate; Attaway H et al.; The ability of 18 gram-negative bacterial isolates to detoxify diisopropyl fluorophosphate, a structural analog of the agents soman and sarin, was investigated . Detoxification by both frozen cell sonicates and acetone powders was assayed by two methods, i.e., the hydrolytic release of fluoride, measured by a fluoride-specific ion electrode, and the disappearance of acetylcholinesterase inhibition in vitro . Frozen cell sonicates for all strains exhibited some activity (F- ion release) . In general, acetone powder preparations produced higher activity than frozen cell sonicates did, and the highest activities were exhibited by strains with known parathion hydrolase activity . Two ranges in activity were observed, low level, ranging from 0.1 to 7.0 mumol/min per g of protein, and high level, detected only in parathion hydrolase-producing strains, from 47 to greater than 300 mumol/min per g of protein . Results indicate that parathion hydrolase was nonspecific in phosphoesterase activity . Also, it was an effective detoxicant at low concentrations and near-neutral pH.

Thromb Res, 1987 Jul 1, 47(1), 37 - 46
Experimental gram-negative septicemia: thromboplastin generation in mononuclear phagocytes from different anatomical sites; Almdahl SM et al.; Rats were subjected to gram-negative septicemia induced by cecal perforation or were sham-operated . Thromboplastin values increased in blood monocytes (40-fold), peritoneal macrophages (115-fold) pleural macrophages (5-fold), splenic macrophages (3-fold), and lung alveolar macrophages (1.4-fold) in septic animals as compared to controls . In septic animals disseminated intravascular coagulation was evidenced by a significant (p less than 0.05) fall in fibrinogen, factor VII, X and platelets . A simultaneous and significant (p less than 0.05) decrease in thromboplastin content of tissue-specimens from lung and spleen was observed in rats with septicemia, whereas increased thromboplastin values were demonstrated in tissue-samples from cecum - the infectious focus . This might reflect mobilization of mononuclear phagocytes in favour of the site of infection.

J Clin Pharmacol, 1987 Jul, 27(7), 491 - 8
The novel therapeutic implications of azlocillin's dose-dependent pharmacokinetics: contributing physiologic mechanisms and a prospective, cross-over designed trial; Whelton A et al.; Azlocillin is an important acylureido penicillin antibiotic for the management of complex gram-negative infections particularly those caused by Pseudomonas species . The current studies demonstrate that it manifests dose-dependent pharmacokinetics during the usual regimens of clinical dosing, that enterohepatic recirculation does not occur and that renal tubular secretion (maximum renal tubular secretory capacity 300 +/- 30 micrograms/min) and hepatic metabolism appear to be the dominant contributors to the dose-dependent nature of azlocillin . The possible therapeutic implications of azlocillin's dose dependency were evaluated by undertaking a six-day randomized, prospective, cross-over design study to evaluate the pharmacokinetic disposition of the drug during a 3-g q4h (typically used in adults) regimen versus a 5-g q8h regimen . By using the area under the serum-time concentration curve (AUC) as the major comparative parameter for these two regimens, the results demonstrate that both regimens provide approximately equal quantitative amounts of the drug systemically as a result of azlocillin's dose dependency . The AUC values, although not therapeutic end points, nonetheless correlate well with clinical response to antibiotic therapy . The 5-g q8h regimen was well tolerated . It is less disruptive for patients, requires half the number of intravenous administrations, 17% less drug, and is more cost effective than the 3-g q4h regimen.

Ann Intern Med, 1987 Jul, 107(1), 36 - 41
The multifactorial basis for hypocalcemia during sepsis . Studies of the parathyroid hormone-vitamin D axis; Zaloga GP et al.; To learn about the pathogenesis of sepsis-associated hypocalcemia, we measured serum ionized calcium concentrations in 60 critically ill patients with bacterial sepsis; 12 (20%) had hypocalcemia . The mortality rate in the hypocalcemic patients with sepsis (50%) was higher than that in the normocalcemic patients with sepsis (29%) . Only patients with gram-negative sepsis became hypocalcemic, and hypocalcemia contributed to hypotension in 7 of the 12 hypocalcemic patients . Serum calcium concentrations returned to normal in each of those patients with sepsis who survived . Hypocalcemia during sepsis occurred in previously normocalcemic patients and was multifactorial in origin, resulting from acquired parathyroid gland insufficiency, renal 1 alpha-hydroxylase insufficiency, vitamin D deficiency, and acquired calcitriol resistance . We conclude that the hypocalcemia of sepsis is associated with a high mortality rate and usually occurs in previously normocalcemic patients who acquire a defect in the parathyroid-vitamin D axis.

Mol Microbiol, 1987 Jul, 1(1), 29 - 36
Sensitivity of Escherichia coli to various beta-lactams is determined by the interplay of outer membrane permeability and degradation by periplasmic beta-lactamases: a quantitative predictive treatment; Nikaido H et al.; In Gram-negative bacteria, beta-lactam antibiotics must overcome two barriers, the outer membrane and the periplasmic beta-lactamase, before they reach the targets of their action, penicillin-binding proteins . Although the barrier property of the outer membrane and catalytic property of the beta-lactamases have been studied and their significance in creating beta-lactam resistance emphasized, the interaction between these two barriers has not been treated quantitatively . Such treatment shows that the sensitivity, to a variety of beta-lactams, of the Escherichia coli K-12 cells containing very different levels of chromosomally coded AmpC beta-lactamase, or a plasmid-coded TEM-type beta-lactamase, can be predicted rather accurately from the penetration rate through the outer membrane and the hydrolysis rate in the periplasm . We further propose a new parameter, 'target access index', which is a quantitative expression of the result of interaction between the two barriers, and reflects the probability of success for the antibiotic to reach the targets.

J Antimicrob Chemother, 1987 Jul, 20(1), 37 - 45
Effect of a diazaborine derivative (Sa 84.474) on the virulence of Escherichia coli; Lam C et al.; The scope of selective inhibition of lipopolysaccharide (LPS) biosynthesis in virulent organisms with a diazaborine derivative (Sa 84.474) as a means to render them avirulent was explored . A serum resistant Escherichia coli 0111:B4 became serum sensitive following its cultivation in vitro in media containing 1.5 mg/l of Sa 84.474, a concentration shown previously to inhibit over 95% of normal LPS biosynthesis in its mutant J5 strain . An encapsulated E . coli 01:K1 was also converted to serum sensitivity . In addition, Sa 84.474-pretreatment increased the efficiency with which the previously resistant organisms were opsonized in normal human serum and subsequently phagocytosed by granulocytes . In vivo, intravenously inoculated, Sa 84.474-pretreated bacteria were rapidly removed from the blood circulation and were significantly (P less than 0.05) less virulent in inducing lethal peritoneal infections in mice (LD50 4.9 +/- 1 X 10(6) cfu) when compared to untreated control bacteria (LD50 2.2 +/- 0.97 X 10(6) cfu) . The results suggest that the LPS plays an important role in the virulence of the two bacterial strains and imply that agents acting in a similar manner but with acceptable selective toxicity might be novel drugs for therapy of Gram-negative bacterial infections.

J Infect, 1987 Jul, 15 Suppl 1, 21 - 8
The use of intravenous immunoglobulin for the treatment of infection: an overview; Yap PL; Immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIgG) is clearly of benefit in primary hypogammaglobulinaemia and related disorders involving antibody deficiency . However, its use in the prevention of infection in other conditions is controversial and needs to be clarified . IVIgG therapy may be of benefit in selected patients with IgG subclass deficiency, and with a proven history of recurrent upper respiratory tract infections . IVIgG therapy may also benefit infants with AIDS and recurrent bacterial infections, but is only rarely of value in cases of adult AIDS . The use of 'normal' IVIgG from unselected blood donors to treat viral infections, infections due to gram negative organisms, or to neutralise endotoxin, is probably not indicated on theoretical and practical grounds, and because of the high cost . IVIgG preparations derived from plasma donations selected for high specific antibody levels to the relevant microorganism will probably be of greater benefit than normal IVIgG in patients with specific infections.

Proc Natl Acad Sci U S A, 1987 Jul, 84(13), 4645 - 9
Transposition of bacteriophage Mu in the Legionnaires disease bacterium; Mintz CS et al.; Legionnaires disease is an acute respiratory disease that is often fatal for immunocompromised patients . The causative agent of this disease, Legionella pneumophila, is a Gram-negative bacterium that is present in a variety of aquatic environments . L . pneumophila is a facultative intracellular parasite; it grows within human phagocytic cells and eventually causes their destruction . In contrast to many other intracellular parasites, L . pneumophila is a Gram-negative bacterium that can be grown in standard microbiological culture medium . To determine the factors that enable this organism to enter, survive, and multiply within human mononuclear phagocytes, we chose bacteriophage Mu, a powerful genetic tool that transposes within the host cell genome, to generate insertion mutations and gene fusions in the Legionella genome . Certain derivatives of Mu are able to generate fusions between target genes and the lac operon from Escherichia coli . We have determined that although Mu is unable to attach to L . pneumophila or complete its life cycle within Legionella, it does transpose within the Legionella genome . Transposition was detected with a mini-Mu phage that carries the lac operon of E . coli.

Eur J Biochem, 1987 Jul 1, 166(1), 131 - 7
The soluble c-type cytochromes from the bacterium Aquaspirillum itersonii . The complete amino acid sequence of the cytochrome c-550; Woolley KJ; A complete amino acid sequence is proposed for the cytochrome c-550 isolated from the gram-negative chemo-organotrophic bacterium Aquaspirillum itersonii . The sequence, a single polypeptide chain of 111 residues, was deduced from the sequences of peptides obtained by tryptic, thermolytic or chymotryptic digestion . The cytochrome shows a high degree of sequence homology with the cytochrome c2 from the photosynthetic bacterium Rhodospirillum rubrum, and the evolutionary implications of this are considered.

Eur J Biochem, 1987 Jul 1, 166(1), 127 - 30
Purification and properties of the soluble cytochromes c-550 and c-556 from the bacterium Aquaspirillum itersonii; Woolley KJ; Two c-type cytochromes were isolated from cells of the gram-negative bacterium Aquaspirillum itersonii grown under low aeration in the presence of nitrate . The major component, cytochrome c-550, was equated with the (single) c-type cytochrome previously reported to be present in this organism {Clark-Walker, G . D . & Lascelles, J . (1970) Arch . Biochem . Biophys . 136, 153-159}, although a significantly higher molecular mass was apparent in the present work . The complete amino acid sequence of this cytochrome is reported in the accompanying paper . A second soluble c-type cytochrome, designated c-556, was also isolated . The molecular mass, isoelectric point, spectrum, midpoint oxidation reduction potential and amino acid composition of this monoheam cytochrome are reported . The possible relationship of this cytochrome to other cytochromes c-556 is discussed.

Jpn J Antibiot, 1987 Jun, 40(6), 1129 - 34
{Fundamental study of amikacin in the newborn}; Hashira S et al.; Amikacin (AMK) is one of the aminoglycoside antibiotics, derived from kanamycin A . It has a broad spectrum against Gram-negative rods but its usefulness is mainly in the efficacy against Gram-negative rods which do not respond to commonly used kanamycin and gentamicin . The efficacy and the safety of AMK have been confirmed in children and mature babies . In the trial reported here, we evaluated AMK in newborn . 1 . AMK was administered to 13 mature and 8 premature babies via intramuscular injection or intravenous drip infusion for 30 minutes or 1 hour and its blood concentrations were determined . These administrations resulted in blood concentrations 4.47-9.67 mcg/ml with dosage levels 2.3 mg/kg (mean 6.92 +/- 1.66 mcg/ml), 5.86-26.1 mcg/ml with 5-6 mg/kg (mean 15.4 +/- 4.63 mcg/ml) and 27.5-37.7 mcg/ml with 7.5 mg/kg (mean 31.0 +/- 4.76 mcg/ml) . Blood half-lives were 1.88 to 9.66 hours, showing longer half-lives in younger subjects . 2 . Exchange transfusion (150-180 ml/kg) was performed in 5 mature babies and the variation of blood concentrations of AMK was studied . The study showed that blood concentrations of AMK after the exchange transfusion were 25.6-41.5% (mean 32.3 +/- 5.4%) of the levels detected before the transfusion.

Am Ind Hyg Assoc J, 1987 Jun, 48(6), 511 - 4
Isolation and identification of gram negative bacteria from raw baled cotton and synthetic textile fibers with special reference to environmental GNB and endotoxin concentrations of textile mill; Gokani VN et al.; The objective of this study was to examine the gram-negative bacterial (GNB) content of Indian raw baled cotton fibers and to compare with the U.S . cottons . Airborne endotoxin also was estimated in the different work places of the mill . On comparison with data on U.S . cottons, GNB content was found to be as high as in U.S . cottons . Moreover, endotoxin concentration of cardroom dust from an Indian cotton mill was found to be significantly (P less than 0.01) higher than in the research laboratory of the same cotton mill as well as in the cardroom of a synthetic mill.

Lab Anim Sci, 1987 Jun, 37(3), 341 - 4
Epidermal capillariasis in South African clawed frogs (Xenopus laevis); Stephens LC et al.; Significant morbidity and mortality of South African clawed frogs, Xenopus laevis, can be caused by parasitism of the epidermis by a capillarid nematode . These worms produce an erosive dermatitis that is complicated by infection with gram-negative microorganisms . The nematode apparently has a direct life cycle that can be completed within the epidermis of the frog . These characteristics are suggested by the lack of an intermediate host and failure to detect visceral migration . Another unique feature of the parasite was the presence of larvated eggs, in utero . Some have named the parasite Capillaria xenopodis, whereas others called it Pseudocapillaroides xenopi to distinguish it form the typical members of the genus Capillaria.

Hepatogastroenterology, 1987 Jun, 34(3), 123 - 6
Circulating lipid A antibodies and their relationship to different clinical conditions of patients with Crohn's disease; Kruis W et al.; Endotoxins have been suggested to be a factor in the pathophysiology of Crohn's disease (CD) . We determined circulating antibodies against lipid A, a component common to endotoxins of gram-negative bacteria . Lipid A antibody titers in 91 patients with CD were significantly higher than in 56 patients with ulcerative colitis and 68 healthy subjects . In active CD lipid A antibodies were higher than in quiescent CD and markedly elevated titers of lipid A antibodies were associated with a severe course of CD . Duration, extent and localisation of CD showed no relationship to antibody titers against lipid A . Patients with prior bowel resection had a tendency towards lower antibody titers in comparison with non-operated patients . After total removal of inflamed bowel tissue, lipid A antibodies frequently disappeared . Medical therapy had different effects: prednisone and sulfasalazine did not influence antibody formation against lipid A, whereas antibody titers dropped significantly after therapy with ampicillin . These results confirm elevated circulating lipid A antibodies in patients with CD . Although it remains unclear whether lipid A antibodies are only an epiphenomenon in CD, on the basis of this clinical study further evidence is provided for the involvement of lipid A in the pathophysiology of CD.

J Bacteriol, 1987 Jun, 169(6), 2881 - 4
Putrescine and cadaverine are constituents of peptidoglycan in Veillonella alcalescens and Veillonella parvula; Kamio Y et al.; Veillonella alcalescens ATCC 17745, a strictly anaerobic, gram-negative small coccus, requires putrescine or cadaverine for growth (M . B . Ritchey, and E . A . Delwiche, J . Bacteriol . 124:1213-1219, 1975) . Both putrescine and cadaverine were demonstrated to be incorporated exclusively into the peptidoglycan layer of V . alcalescens ATCC 17745 . V . parvula GAI 0574 also proved to contain putrescine as a component of peptidoglycan . The primary chemical structure of the peptidoglycan common to the two Veillonella species is N-acetylglucosamine-N-acetylmuramic acid-L-alanine-D-glutamic acid gamma-meso-diaminopimelic acid-D-alanine . Putrescine or cadaverine links covalently to the alpha-carboxyl group of the D-glutamic acid residue of the peptidoglycan is necessary for normal cell growth . In V . alcalescens ATCC 17745, above 40% saturation at cadaverine linked to the alpha-carboxyl group of the D-glutamic acid residue of the peptidoglycan is necessary for normal growth.

Brain Behav Immun, 1987 Jun, 1(2), 159 - 72
Significance of increased secretion of glucocorticoids in mice and rats injected with bacterial endotoxin; Nakano K et al.; Injection of mice or rats with lipopolysaccharide (LPS) is associated with an increased secretion of glucocorticoids . The high level of mortality following injection of LPS that is noted in adrenalectomized rats can be reversed by dexamethasone or corticosterone . That histamine may be an endogenous mediator of the release of corticosterone caused by LPS is suggested by an attenuation of this corticosterone response by promethazine, an H1 antihistamine . Additional support that LPS-dependent glucocorticoid secretion is mediated, in part, by histamine, is suggested by spleen cell transfer studies revealing differences in the induction of histidine decarboxylase (HDC) synthesis and corticosterone release by the C3H/HeN and C3H/HeJ strains of mice that are differentially sensitive to LPS effects . These and other data on increased levels of histamine and HDC during mitogen-induced lymphocyte blastogenesis, as well as experiments revealing immunomodulatory effects of histamine and histamine agonists and antagonists on lymphocyte blastogenesis, are consistent with the hypothesis that following infection with gram-negative bacteria, the histamine-induced increase in glucocorticoid secretion results in inhibition of HDC in splenocytes, a concomitant attenuation of histamine production, and a resulting return to immune homeostasis.

Biochem J, 1987 Jun 1, 244(2), 393 - 9
Bacterial killing by complement . C9-mediated killing in the absence of C5b-8; Dankert JR et al.; The ability of serum complement to kill Gram-negative bacteria requires assembly of the membrane attack complex (MAC) on the cell surface . The molecular events that lead to cell killing after MAC assembly are unknown . We have investigated the effect of C9 on bacterial survival in the presence and absence of its receptor, the C5b-8 complex, on the outer membrane . A fluorescence assay of the membrane potential across the inner bacterial membrane revealed that addition of C9 to cells bearing the performed C5b-8 complex caused a rapid and complete dissipation of the membrane potential . No fluorescence change was observed in serum-resistant strains of Escherichia coli . Addition of trypsin, after C9 was bound to C5b-8, did not rescue the cells from the lethal effects of C9 . Furthermore, assays of cell killing kinetics and C9 binding indicate that formation of tubular poly(C9) is not required for killing . When C9 was introduced into the periplasmic space in the absence of its receptor by means of an osmotic shock procedure, cell killing occurred . Other proteins, such as C8 or serum albumin, were not toxic, and C9 was ineffective against two resistant strains . The results presented here and previously {Dankert & Esser (1986) Biochemistry 25, 1094-1100}, when considered together, indicate that the 'lethal unit' in complement killing of some Gram-negative bacteria is a C9-derived product that acts by dissipation of cellular energy.

J Med Virol, 1987 Jun, 22(2), 189 - 98
Microbial structures in a patient with sporadic non-A, non-B fulminant hepatitis treated by liver transplantation; Fagan EA et al.; Double-shelled virus-like particles (60 nm) and long cytoplasmic tubular structures were found in the cytoplasm of hepatocytes from areas of collapsed and regenerating areas of hepatectomised liver in a 13-year-old boy who received a liver graft for fulminant hepatitis attributed to sporadic non-A, non-B hepatitis . The patient died on the ninth postoperative day from acute graft failure . Although virus-like particles were not found, instead, gram-negative rods were identified in the necrotic graft and the most likely cause of death was a gram-negative septicaemia with a Shwartzman-like reaction localized to the liver.

Am J Clin Pathol, 1987 Jun, 87(6), 739 - 44
Ultrastructural observations in cat scratch disease; Osborne BM et al.; Because the causative bacterium of cat scratch disease has not been definitively cultured or fully characterized, the authors have studied its ultrastructure in lymph node biopsies from two patients using glutaraldehyde-fixed tissue . In both specimens, the organisms were invariably extracellular, forming small groups within bundles of collagen fibrils . Their appearance was similar in necrotic and viable regions of the nodes, although in the latter sites they could not be identified by light microscopic examination with the Warthin-Starry stain . The bacteria were pleomorphic rods, and, despite faint gram-negative staining, their walls were consistently thick and homogeneous.

J Clin Pharmacol, 1987 May-Jun, 27(5), 419 - 24
Predictive performance of Sawchuk-Zaske and Bayesian dosing methods for tobramycin; Rodvold KA et al.; We evaluated the reliability of pharmacokinetic parameter estimations determined by the Sawchuk-Zaske method and by a Bayesian method for predicting steady-state tobramycin concentrations on day 4 and day 10 of therapy in 30 patients treated for gram-negative infections . We also assessed the effect of using only trough tobramycin concentrations on the predictive performance of the Bayesian method . The mean estimation of tobramycin volume of distribution was significantly different for the Bayesian methods compared with the Sawchuk-Zaske methods when the same number of L/kg) . Comparing the Bayesian and Sawchuk-Zaske methods when the same number of serum concentrations was available, the Bayesian method overpredicted peak concentrations on day 4 of therapy . When only trough concentration data were used, the Bayesian method significantly overpredicted peak concentrations compared with the Sawchuk-Zaske method on days 4 and 10 of therapy . Each method predicted steady-state trough concentrations without significant differences in bias or accuracy . The Bayesian method may be useful in providing aminoglycoside dosing recommendations.

Zh Mikrobiol Epidemiol Immunobiol, 1987 May, (5), 3 - 9
{The problem of predicting new species of microorganisms (the example of nonfermenting gram-negative microorganisms)}; Kalina GP; Various microbial species, embraced by the genera, have been found to correspond to their phylogeny by the types of nutrition and the levels of pathogenicity . A relationship between the types of nutrition and the levels of parasitism and pathogenicity has been revealed . The results of analysis make it possible to assume, with a great degree of probability, the existence of new species (subspecies, variants) in the environment and/or as agents of diseases of unclear etiology.

Antimicrob Agents Chemother, 1987 May, 31(5), 805 - 7
Clinical efficacy and levels of ciprofloxacin in tissue in patients with soft tissue infection; Licitra CM et al.; The clinical efficacy of ciprofloxacin was evaluated with 21 patients with soft tissue infection due mainly to gram-negative aerobic bacteria . Clinical cure was noted in 16 patients (76%), and clinical improvement was noted in the remaining 5 patients (24%) . In addition, levels of ciprofloxacin were measured in the sera and tissues of 11 patients . Mean concentrations in tissue averaged 1.75 times the levels in serum . Ciprofloxacin should provide serum and soft tissue concentrations above the MICs for most gram-negative aerobic bacteria.

Pediatr Infect Dis J, 1987 May, 6(5), 461 - 6
Five years of experience with the exclusive use of amikacin in a neonatal intensive care unit; Powell KR et al.; From November 1, 1980, to December 31, 1985, 3959 infants were admitted to the neonatal intensive care unit and 2385 infants (60%) received 2791 courses of aminoglycoside therapy . Aminoglycoside use totaled 16,279 patient days of which 16,070 (98.7%) were with amikacin . From November 1, 1980, to January 31, 1983, 1017 pairs of pre- and posttreatment endotracheal or pharyngeal specimens yielded 318 Gram-negative bacteria isolates . From November 1, 1980, to December 31, 1985, Gram-negative bacteria were isolated from 381 clinical specimens . Of the 318 surveillance and 380 clinical isolates tested, 285 (90%) and 358 (94%), respectively, were susceptible to amikacin . Amikacin resistance did not increase during the study . Amikacin-resistant organisms were isolated more frequently from patients receiving multiple courses than those receiving single courses of amikacin and resistant organisms were not usually found before the administration of amikacin . None of the 15 amikacin-resistant isolates made 6'-N-aminoglycoside acetyltransferase and 3 isolates took up only small amounts of radiolabeled amikacin, suggesting that resistance was due to decreased permeability . The extensive use of amikacin in a neonatal intensive care unit for over 5 years did not result in an increase of amikacin-resistant Gram-negative bacteria.

Am J Physiol, 1987 May, 252(5 Pt 2), R809 - 21
Ion transport in circulatory and/or septic shock; Sayeed MM; This review surveys investigations of membrane ion transport in animals in hemorrhagic, endotoxic, or bacteremic shock . The focus of the review is on ion transport studies in the skeletal muscle and liver . Skeletal muscle Na+-K+ transport alterations have been shown during the induction of shock via hemorrhage, endotoxin, or live Gram-negative bacteria in the rodent, canine, and primate species . These alterations include impairment of active cellular K+ accumulation, increased permeability to Na+ and Cl-, and membrane depolarization . The ion transport alterations in the skeletal muscle are compatible with movement of extracellular fluid into the intracellular compartment . Such fluid movements can potentially lead to decreases in circulating plasma volume and thus to circulatory deficits in shock . Studies in the liver of rats subjected to hemorrhagic or endotoxic shock indicated the failure of electrogenic Na+ pump . Although the hepatic cellular membrane permeability to Na+ relative to permeability to K+ appeared unaltered in hemorrhagic shock, endotoxic shock caused an increase in permeability to Na+ . Hepatic cellular Ca+ regulation also appeared to be adversely affected during endotoxic shock . Alterations in hepatic Na+-K+ transport and Ca+ regulation could contribute to impairment in hepatic glucose production during shock . Although mechanisms of altered membrane ion transport during shock states remain unknown, such changes could occur prior to any substantial loss of cellular metabolic energy.

Int J Clin Pharmacol Ther Toxicol, 1987 May, 25(5), 282 - 8
Use of ceftazidime in the treatment of otorhinolaryngoiatric bacterial infections; Vellucci A et al.; Within the framework of an investigation into otorhinolaryngoiatric bacterial infections in Italy conducted in 1159 patients (607 with otitis media, 354 with pharyngo-tonsillitis and 198 with sinusitis), 124 ceftazidime-treated subjects (92 with otitis media, 22 with pharyngo-tonsillitis and 10 with sinusitis) were observed . The authors report the examination of a number of microbial isolates obtained in the various forms of otorhinolaryngoiatric bacterial infection . Gram-negative organisms were found as causative agents in such diseases, particularly in otitis media . Bacterial resistance to ceftazidime was assessed in all 1159 cases and proved relatively infrequent (3.6%) and markedly less than the detected resistance to other antibiotics (10.7% resistance to cefotaxime, 35% resistance to ampicillin, 43% resistance to penicillin) . Ceftazidime, used mainly in otitis media, showed very substantial clinical efficacy with positive results in as many as 97% of cases treated, which is particularly significant, if one considers that roughly 64% of the infections were caused by "difficult" gram-negative bacteria (49% by Pseudomonas).

J Clin Microbiol, 1987 May, 25(5), 856 - 8
Correlation of cerebrospinal fluid endotoxinlike activity with clinical and laboratory variables in gram-negative bacterial meningitis in children; Dwelle TL et al.; Detection of endotoxinlike activity in cerebrospinal fluid by Limulus amebocyte lysate gelation has been suggested as a useful technique for the diagnosis of gram-negative bacterial meningitis . We prospectively screened 1,503 cerebrospinal fluid specimens with a Limulus amebocyte lysate microassay . The limit of sensitivity of the assay was 0.01 ng/ml . All specimens that were positive for endotoxinlike activity were subjected to confirmatory retesting, after which 38 (86%) remained positive . Comparison with available culture results revealed that 33 of 38 specimens (86%) were culture positive; 3 of the 5 culture-negative specimens were from patients on therapy for gram-negative bacterial meningitis, and 1 was from a neonate . The overall specificity of confirmed positive tests was 99.5%, with a positive predictive value of 97.3% . There was one false-negative specimen, giving an overall sensitivity of 97.3% and a negative predictive value of 99.9% . Endotoxinlike activities of greater than or equal to 150 ng/ml correlated with present illness of less than 2 days' duration (P = 0.024), elevated cerebrospinal fluid protein (P less than 0.05), and seizures (P = 0.004); levels of greater than or equal to 3,000 ng/ml correlated with neutropenia (P = 0.032), and levels of greater than or equal to 3.2 X 10(6) ng/ml correlated with death (P = 0.001) . We conclude that the Limulus amebocyte lysate microslide gelation test has prognostic value as a sensitive, specific, simple, inexpensive screening test for gram-negative bacterial meningitis.

Mol Gen Mikrobiol Virusol, 1987 May, (5), 44 - 6
{Improved method of lipopolysaccharide isolation from gram-negative bacteria}; Kul'shin VA et al.; A modification of the traditional method for lipoplysaccharide isolation from the cells of grammnegative bacteria was elaborated on the basis of extraction by the hot water solution of phenol (the method of Westfahl) . To make the method simpler and to raise the yield of the product it was proposed to use the water-phenol extract without its division for plases . The nucleic acids are eliminated by precipitation from dialyzed extract at pH 3,2-3,4 achieved by addition of acetic acid . The comparative isolation of lipopolysaccharides by the classic and modified methods has confirmed the advantages of a new technique.

Proc Soc Exp Biol Med, 1987 May, 185(1), 6 - 15
The inhibition of endotoxin-induced local inflammation by LDH virus or LDH virus-infected tumors is mediated by interferon; Heremans H et al.; The footpad swelling reaction induced by local injection of S . marcescens lipopolysaccharide was found to be inhibited in mice given a transplantable tumor (TA3) or cell-free ascitic fluid from tumor-bearing mice . The tumor was shown to contain LDH virus, which is known to cause inapparent persistent infections in mice . Monoclonal antibodies directed against protein VP3 of the LDH virus could partially abrogate the anti-inflammatory effect of the TA3-ascitic fluid, and, conversely, the anti-inflammatory effect could be obtained by LDH virus isolated from the tumor and reproduced by serial passage of cell-free fluids . Inhibition of the footpad reaction was seen in the acute but not in the chronic phase of LDH virus infection, suggesting that the anti-inflammatory effect might be due to endogenous interferon (IFN) which, similarly, was only detectable in the acute phase . Newcastle disease virus, another potent interferon inducer, had a similar inhibitory effect on the footpad reactivity . Moreover, the inhibitory effect of LDH virus infection could partially be abrogated by administration of a polyclonal antibody directed against murine IFN-alpha,beta . Finally, passively administered natural murine IFN-alpha,beta or recombinant murine IFN-alpha 1 (but not recombinant murine IFN-beta) was found to cause inhibition of the footpad reaction . Since Gram-negative bacteria and their lipopolysaccharides have the ability to induce a systemic interferon response, our findings suggest that this interferon may play a modulatory role in local inflammation caused by these bacteria . Our findings also open a new perspective for interferon therapy of certain inflammatory reactions to bacterial infections.

J Clin Invest, 1987 May, 79(5), 1421 - 30
Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of lipopolysaccharides; Pollack M et al.; Epstein-Barr virus (EBV)-transformed human B lymphocytes were fused with a murine-human heteromyeloma to produce stable hybrid cell lines that secreted human monoclonal antibodies (mAbs) of the IgM class that recognized conserved epitopes in the core-lipid A region of lipopolysaccharides (LPS) . Three of the mAbs reacted with epitopes on the lipid A moiety, while a fourth recognized a determinant in the core oligosaccharide . The lipid A-specific mAbs cross-reacted with heterologous rough LPS and with lipid As released by acid hydrolysis of different intact (smooth) LPS . Carbohydrate groups in the O-side chain and core oligosaccharide of isolated, smooth LPS restricted antibody access to antigenic sites on lipid A . Yet, one lipid A-reactive mAb recognized its epitope on the surfaces of a variety of intact bacteria . These findings confirm the presence of highly conserved epitopes in the core-lipid A complex and prove the existence of human B cell clones with the potential for secreting high avidity IgM antibodies that react with these widely shared determinants . Such human mAbs might provide protective activity against disease caused by diverse gram-negative bacteria.

Biochemistry, 1987 Apr 21, 26(8), 2139 - 49
Interaction of polymyxin B nonapeptide with anionic phospholipids; Kubesch P et al.; The interaction of polymyxin B nonapeptide (PMBN) and polymyxin B (PMB) with the anionic phospholipids phosphatidylserine (PS), dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidic acid (DPPA), and 1:1 mixtures (w/w) of DPPA and distearoylphosphatidylcholine (DSPC) was studied by calorimetry, electron spin resonance, and fluorescence spectrometry, electron microscopy, and fusion and leakage assays . The phase transition temperatures of DPPA and DPPG were very similar when bound to PMB or PMBN, indicating that the lipids are in a similar state when bound to the cationic peptides . Both PMB and PMBN caused the interdigitation of DPPG bilayers, suggesting that the penetration of hydrophobic side chains from a peptide bound electrostatically on the surface is sufficient to induce this phenomenon . Stopped-flow experiments revealed that PMBN and PMB induced the fusion of small unilamellar PS and large unilamellar DPPA-DSPC vesicles . The aggregation of vesicles was found to be diffusion-controlled process; the subsequent fusion took place with a frequency of 10(2)-(5 X 10(2} s-1 for small vesicles and 1-100 s-1 for large vesicles . The freeze-fracture replicas of the PMB-treated vesicles displayed 12-50-nm depressions on several superimposed bilayers, indicating the formation of stable lipid-PMB domains . Since the incubation with PMBN produced similar depressions only if the specimens were fixed, PMBN-induced domain formation seems to be a reversible rapid process . The differences in the phospholipid-peptide interactions are correlated with the differences in the physiological action of the antibiotic PMB and the nonbactericidal PMBN on the cell envelope of Gram-negative bacteria.

Scand J Gastroenterol, 1987 Apr, 22(3), 313 - 20
Impact of experimental endogenous gram-negative peritonitis on the pancreas of the rat as evaluated by cationic trypsin-like immunoreactivity in peritoneal fluid and serum and by electron microscopy of pancreatic tissue; Florholmen J et al.; Endogenous gram-negative peritonitis leading to septic shock was induced in rats by a defined perforation of the coecum . Cationic trypsin-like immunoreactivity (CTLI) was measured in peritoneal fluid and serum by a radioimmunoassay method . Five, 10, and 15 h after the coecal perforation, CTLI in peritoneal fluid was significantly higher than before the coecal perforation and also higher than in the corresponding control rats . Moreover, CTLI in serum was under the same conditions significantly higher 10 and 15 h after the induction of peritonitis . Gel chromatography of peritoneal fluid and serum during peritonitis showed free CTLI and CTLI bound to both alpha-1-antitrypsin and alpha-2-macroglobulin, whereas only free CTLI could be detected in serum from control rats . These findings were accompanied by local ultrastructural changes in the acinar cells as evaluated by electron microscopy . The pathophysiologic implications of the findings are discussed.

Scand J Gastroenterol, 1987 Apr, 22(3), 295 - 300
Spontaneous bacterial peritonitis in cirrhosis . Incidence, diagnosis, and prognosis; Almdal TP et al.; Among 342 consecutive patients admitted to the hospital with cirrhosis of the liver 68 (17%) had ascites and had a diagnostic paracentesis performed . Fourteen episodes of peritonitis were diagnosed in 13 patients, which is an overall incidence of peritonitis of 19% . The incidence of peritonitis was 36% in patients with hepatic encephalopathy and 10% in patients without hepatic encephalopathy (P less than 0.01) . In all except one case the infecting organism was most likely of enteric origin--that is, gram-negative or anaerobic species . The infected patients had lower mean ascites pH and higher mean ascites leukocyte and polymorphonuclear cell counts than non-infected patients . However, there was a considerable overlap between the two groups, and the diagnostic sensitivity did not exceed 65% for any of these three features . The survival of infected patients without encephalopathy was 33%, which was significantly lower (P less than 0.05) than that the 89% for non-infected patients . In patients with encephalopathy the survival was identical for infected and non-infected patients.

J Antimicrob Chemother, 1987 Apr, 19(4), 467 - 73
In-vivo effects of clindamycin on polymorphonuclear leucocyte phagocytosis and killing of gram-negative organisms; Bassaris HP et al.; Polymorphonuclear leucocyte (PMNL) phagocytosis and killing were evaluated in ten healthy volunteers who had received 600 mg of clindamycin intramuscularly . Serum obtained 3 h after the administration of clindamycin significantly increased PMNL phagocytosis and killing of Gram-negative aerobic organisms . Serum obtained at 12 and 24 h after the administration of the drug did not induce a significant increase in PMNL phagocytosis and killing . The administration of clindamycin had no direct effect on the PMNLs in terms of their phagocytic and bactericidal function . These results demonstrate serum-associated augmentation of PMNL function by clindamycin in vivo which may be of potential clinical benefit in the outcome of infections.

J Immunol, 1987 Apr 1, 138(7), 2143 - 8
Induction of colony stimulating factor in vivo by recombinant interleukin 1 alpha and recombinant tumor necrosis factor alpha 1; Vogel SN et al.; In response to a potent inflammatory challenge, such as Gram-negative endotoxin, a number of cytokines are induced that, in turn, mediate many of the pathophysiologic alterations associated with endotoxicity . In this study, we have observed two endotoxin-associated monokines, recombinant interleukin-1 alpha (rIL 1 alpha) and recombinant tumor necrosis factor alpha (rTNF alpha), to induce colony stimulating factor (CSF) in vivo . The CSF activities produced in response to rIL 1 alpha or rTNF alpha gave rise to a mixture of granulocyte-macrophage colonies and were induced in a dose- and time-dependent fashion, peaking within 3 hr of cytokine injection (preceding peak CSF induction by endotoxin by several hours) . Combined injection of suboptimal concentrations of rIL 1 alpha and rTNF alpha were additive, and simultaneous injection of optimal concentrations of each failed to increase CSF levels over that observed with either cytokine alone . Unlike endotoxin, neither cytokine induced interferon in vivo . These findings extend our understanding of the cytokine cascade that is operative in an inflammatory response and may account for many of the observed hematopoietic alterations that accompany inflammation.

Orthop Rev, 1987 Apr, 16(4), 246 - 54
A review of antibiotic prophylaxis for open fractures; Antrum RM et al.; A review of the literature strongly supports the use of antibiotic prophylaxis in open fracture management . Because of their broad spectrum of activity, cephalosporins are the drugs of choice in cases of orthopaedic trauma . The extent of the injury determines the appropriate agent and the length of time it should be given . Patients with Type 1 or Type 2 fractures require only brief treatment (one preoperative and two postoperative doses) with an agent that has good antistaphylococci activity . Cephalothin, cefazolin, cefamandole or cefuroxime are recommended . Type 3 fractures present a much greater problem because of the risk of gram-negative infection . The marked activity of cefuroxime, cefamandole, and cefotaxime against these organisms recommends their use in such cases . Combination regimens with aminoglycosides require further study to define added efficacy and to define appropriate dosing regimens . We advocate that antibiotic prophylaxis should be given as soon as possible to all patients with open fractures and Type 3 fractures, and that prophylaxis should continue until 48 hours after adequate soft tissue coverage is achieved.

Acta Chir Scand, 1987 Apr, 153(4), 287 - 90
Splenectomy in the rat . Immediate and late effects on clearance of gram-negative bacteria and on monocyte activation as expressed by thromboplastin synthesis; Almdahl SM et al.; Young rats (weight 190-200 g) were subjected to splenectomy or sham laparotomy and gram-negative bacteraemia was induced by caecal perforation or by injection of viable Escherichia coli intraperitoneally (10(9) bacteria) or intravenously (2 X 10(8} . Clearance of bacteria was significantly less in the splenectomized than in the sham-laparotomized rats, irrespective of the mode of microbial inoculation . Monocyte thromboplastin activity, shown to be a sensitive indicator of gram-negative bacterial presence, was heightened in the asplenic rats . When the infectious challenge was made 15 weeks postoperatively, however, no significant difference in bacterial clearance or in monocyte thromboplastin values was found between splenectomized rats and controls . Nor was increased susceptibility to gram-negative bacteria found in asplenic rats when both operation (splenectomy vs . sham laparotomy) and bacterial challenge were performed at a late age (weight 530-580 g) . The postsplenectomy clearance of gram-negative bacteria thus seemed to be age-dependent.

Acta Chir Scand, 1987 Apr, 153(4), 283 - 6
Effect of antibiotics on gram-negative sepsis in the rat . Lack of endotoxin burst; Almdahl SM et al.; Endotoxin and monocyte thromboplastin activity were evaluated in rats with gram-negative septicaemia induced by caecal perforation or intravenous Escherichia coli challenge and treated with antibiotics or placebo . Endotoxin burst was not detected in either form of septicaemia during antibiotic treatment . Thromboplastin synthesis in monocytes is known to be stimulated by endotoxin, but the rats showed no increase of monocyte thromboplastin activity after antibiotic treatment, which constituted further evidence against the concept of massive endotoxin liberation during antibiotic therapy for gram-negative septicaemia.

Genetics, 1987 Apr, 115(4), 619 - 25
Mode of replicon fusion mediated by the duplicated insertion sequence IS21 in Escherichia coli; Reimmann C et al.; The insertion sequence IS21 (2.1 kb) originating from the broad-host-range IncP plasmid R68 transposes infrequently; by contrast, the IS21 tandem repeat found on the derivative R68.45 is highly active in transpositional mobilization of other replicons in a variety of Gram-negative bacteria . The mobilized plasmids are joined to R68.45 by single IS21 copies in direct orientation . The formation of IS21 tandem duplications was observed in cointegrates between R68.45 and pBR325::IS21 and also in an RP1::IS21 plasmid derivative in which a segment located between two directly repeated copies of IS21 was deleted spontaneously . We speculate that IS21 tandem repeats can arise when the termini of two IS21 elements are specifically joined in a transposition or deletion event . A resistance gene flanked by two IS21 elements in direct orientation did not behave as a transposon . The omega fragment carrying transcription and translation stop signals was inserted into various sites of the IS21 tandem repeat; in this way it could be shown that the left IS21 element (which is next to the kanamycin resistance gene in R68.45) was 100 times more active in cointegrate formation than was the right-hand element . Cointegrates between the conjugative plasmid R751 and pBR325 derivatives carrying IS21 and IS21::omega in tandem contained a single IS21 at one replicon junction and a single IS21::omega at the other . In the IS21 duplications the inner IS21 ends were preferentially recognized (presumably by IS21 transposase), whereas the outer termini were not required for cointegrate formation . Based on these findings a conservative (simple) pathway of transposition is proposed for R68.45 and other plasmids with an IS21 tandem repeat.(ABSTRACT TRUNCATED AT 250 WORDS)

Infect Immun, 1987 Apr, 55(4), 916 - 22
Purification and characterization of serotype 6 fimbriae from Bordetella pertussis and comparison of their properties with serotype 2 fimbriae; Cowell JL et al.; Fimbriae were removed from Bordetella pertussis (serotype 1.3.6) by mechanical shearing and purified by precipitation with ammonium sulfate, pH-dependent precipitation at pH 7.4, followed by two successive extractions of the precipitated fimbriae with 4 M urea . By electron microscopy, the precipitated fimbriae appeared as aggregated bundles of long, relatively straight filaments which were disaggregated to individual flexuous filaments at pH 10.5 . These purified fimbriae were identified as serotype 6 agglutinogens, since antibody to the purified fimbriae agglutinated B . pertussis strains serotyped as 1.3.6, 1.2.3.6, or 1.2.3.4.6 but did not agglutinate strains of serotype 1.2.3.4, 1.2.3, or 1.3 . In contrast, antibody to serotype 2 fimbriae only agglutinated B . pertussis strains containing serotype 2 agglutinogen . Purified type 6 and 2 fimbriae were found to be weakly cross-reactive by enzyme-linked immunosorbent assay, using polyclonal antibody to each type of fimbria . In an immunoblot assay, polyclonal antibodies to a 22,000-dalton subunit of fimbriae from B . bronchiseptica reacted strongly with the type 2 fimbrial subunit of B . pertussis, but only weakly with the type 6 subunit . When subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein subunit of the type 6 fimbriae migrated with a molecular weight of 21,500, whereas the type 2 fimbrial subunit had a molecular weight of 22,000 . The two types of subunits had similar amino acid compositions and showed amino-terminal sequence homology in 15 of 21 amino acids . The amino-terminal amino acid sequences of the B . pertussis fimbriae were distinct from those reported for fimbriae from other gram-negative bacteria . Neither the type 6 nor the type 2 fimbriae caused hemagglutination when assayed with several types of erythrocytes.

Biochem Biophys Res Commun, 1987 Mar 30, 143(3), 1063 - 8
A 2-deoxy analogue of KDO as the first inhibitor of the enzyme CMP-KDO synthetase; Claesson A et al.; The two KDO analogues 2,6-anhydro-3-deoxy-D-glycero-D-galacto-octonate and 2,6-anhydro-3-deoxy-D-glycero-D-talo-octonate were synthesized and tested as inhibitors of the enzyme CTP:CMP-deoxyoctulosonate cytidylyltransferase (CMP-KDO synthetase) from Gram-negative bacteria . Only compound 4, the 2-deoxy analogue of beta-KDO-pyranose, was found to be an inhibitor with a Ki of 3.9 microM.

Biochim Biophys Acta, 1987 Mar 19, 923(3), 463 - 9
Purification and properties of a pepstatin-insensitive carboxyl proteinase from a gram-negative bacterium; Oda K et al.; A carboxyl proteinase was found in the culture filtrate of a Gram-negative bacterium . The optimum for the action of the purified enzyme was approx . pH 3 and its caseinolytic activity was not inhibited by carboxyl proteinase inhibitors, such as pepstatin, Streptomyces pepsin inhibitor and diazoacetyl-DL-norleucine methyl ester . 1,2-epoxy-3-(p-nitrophenoxy)propane modified the enzyme with concomitant loss of its enzyme activity . The enzymatic and physicochemical properties of the enzyme were compared with those of known pepstatin- and diazoacetyl-DL-norleucine methyl ester-insensitive carboxyl proteinases previously reported . To our knowledge, this is the first carboxyl proteinase isolated from bacteria.

Am Rev Respir Dis, 1987 Mar, 135(3), 671 - 5
Increased salivary elastase precedes gram-negative bacillary colonization in postoperative patients; Dal Nogare AR et al.; The upper airway epithelium is coated with fibronectin, a glycoprotein that covers receptor sites for gram-negative bacteria and prevents them from colonizing the oropharynx . We investigated the identity of salivary proteolytic enzymes capable of degrading fibronectin in a group of 16 patients who had elective cardiac surgery . Six patients became colonized with gram-negative bacteria (Group C) and 10 did not (Group NC) . Salivary elastase activity was low in both groups preoperatively . Twenty-four hours after surgery, salivary elastase activity increased in Group C, and it remained elevated at 48 and at 72 h . Fibronectin digestive activity of the saliva of patients in Group C was also increased within 24 h of surgery, and salivary elastase and fibronectin digestive activity were highly correlated (r = 0.86, p less than 0.001) . Enzyme inhibition experiments showed that most of the fibronectin digestive activity was due to elastase from polymorphonuclear cells (PMN), and the molecular weight of the salivary enzyme digesting fibronectin was 30,000 daltons (similar to the molecular weight of elastase) . Levels of antileukoprotease, the major elastase inhibitor in saliva, were normal in patients with increased elastase activity . We conclude that salivary elastase is of PMN origin, increases prior to gram-negative bacillary colonization of the pharynx, and is responsible for most of the fibronectin digestive activity of the saliva.

EMBO J, 1987 Mar, 6(3), 823 - 31
Signal peptide amino acid sequences in Escherichia coli contain information related to final protein localization . A multivariate data analysis; Sjostrom M et al.; With few exceptions, the signal peptides from proteins inserted into, or translocated through, the membranes of gram-negative bacteria or the endoplasmic reticulum of eukaryotes have no sequence homologies . Therefore these signal peptides have not been considered to contain information related to the different final localizations of the proteins . In this study, 43 signal peptide amino acid sequences from proteins with different final localizations in Escherichia coli have been subjected to a multivariate data analysis . Each amino acid residue was characterized by 20 physico-chemical properties, yielding a multivariate property profile for each peptide . The similarities/dissimilarities in the property profiles for the signal peptides from different classes were compared with each other by generating few-dimensional partial least squares (PLS) discriminant plots . With this approach, signal peptides from proteins localized to the periplasmic space (PS), the outer membrane (OM), and the extracellular surroundings (excreted proteins), were separated into distinct groups . Signal peptides from pili proteins were not separated from the OM signal peptides and only partly from the PS signal peptides, but were clearly different from the signal peptides of the excreted proteins . Signal peptides from inner membrane proteins were similar to those of the PS peptides . The size and the hydrophobicity of different peptide segments were responsible for the separation of the signal peptide classes . For example, the hydrophobicity of the N-terminal segment of the signal peptides increased with an increased distance from the cytoplasm of the final localization for the corresponding proteins . Thus, many signal peptides from proteins with different final localizations in E . coli have different discernible physico-chemical profiles.

Infect Immun, 1987 Mar, 55(3), 668 - 73
Prophylactic administration of interleukin-2 protects mice from lethal challenge with gram-negative bacteria; Chong KT; Prophylactic administration of recombinant human interleukin-2 (IL-2) in mice enhanced survival and produced complete recovery from an otherwise lethal acute bacterial infection . IL-2 was administered as a single intraperitoneal or intravenous bolus dose to CDI mice 18 h before challenge with a lethal dose of a clinical isolate of Escherichia coli type O2 (minimal 100% lethal dose, 6 X 10(7) CFU per mouse) . At IL-2 dosages of 7 X 10(6) U/kg, 90% of treated CDI mice survived as compared to 0% for the excipient buffer control animals (P less than 0.001) . This protective effect was also demonstrable in immune-deficient beige mice . The IL-2 effect was dose dependent; protection was consistently observed in mice pretreated with IL-2 at doses ranging from 1.8 X 10(6) to 7 X 10(6) U/kg . However, at 3.5 X 10(5) U/kg the protective effect was more variable . The route of administration of IL-2 was shown to play an important role; when IL-2 and challenge bacteria were given by the same route (either intravenously or intraperitoneally), protection was readily observable, but when IL-2 and challenge bacteria were given by different routes, little or no protective effect was observed . The protective effect was fully inducible as early as 1 h after IL-2 administration and was effective against various strains of gram-negative bacteria, indicating that the probable mode of action represents control of the establishment of infection by increased activity of the nonspecific host defense mechanisms . The IL-2 effect was abrogated by the administration of carrageenan, suggesting a possible role of macrophages . These data demonstrate that IL-2 may be a potentially useful adjunct for the prophylaxis of bacterial infections in both clinical and veterinary medicine.

Gan To Kagaku Ryoho, 1987 Mar, 14(3 Pt 1), 674 - 9
{Cefmenoxime or piperacillin plus amikacin . A prospective randomized comparison of empiric antibiotic therapy of febrile granulocytopenic cancer patients}; Sampi K et al.; Cefmenoxime plus amikacin was compared in a prospective randomized trial with our standard regimen of piperacillin plus amikacin as an empiric therapy for fever in patients with granulocytopenia . Initial profound granulocytopenia (fewer than 100/mm3 mature granulocytes) was present in approximately 45% of the patients in trial of both treatment groups . Of 53 microbiologically and clinically documented infections treated with piperacillin plus amikacin, 36 (68%) showed improvement . Of 48 microbiologically and clinically documented infections treated with cefmenoxime plus amikacin, 23 (48%) showed improvement . The response rate for gram-negative infections treated with cefmenoxime plus amikacin was lower than that for infections treated with piperacillin plus amikacin . Toxicity was minimal, with an equivalent incidence of skin rash, diarrhea and hepatic dysfunction . Although clinical efficacy of the combination of piperacillin plus amikacin may be superior to cefmenoxime plus amikacin therapy, this study demonstrated no statistically significant differences.

Infection, 1987 Mar-Apr, 15(2), 146 - 52
{Antibodies to lipoid A in the treatment of septic shock}; Jaspers L et al.; The protective effect of high-titer anti-lipid A hyperimmune globulin with respect to the course of the disease and the mortality rate was studied in patients with septicemia verified by positive blood cultures . Six patients were treated with anti-lipid A in an open study . Dramatic improvement in fever curves and clinical condition in some of the patients encouraged us to start a randomized double blind study . So far, 17 patients have entered the study, 16 of whom were evaluable . Immediately after a positive blood culture was found, patients received either high doses of anti-lipid A or placebo (saline solution) on two subsequent days . Before and after each infusion blood samples were taken in order to assess serum bactericidal activity and anti-lipid A titers . Because of the still small numbers of patients the results of both studies were summarized . In all patients treated with anti-lipid A clear-cut increases in anti-lipid A titers were shown . Patients with repeated gram-negative infections showed higher median anti-lipid A titers than patients without such a history . The patients treated with anti-lipid A immune globulin ran a significantly milder course than the placebo group . The severe signs of septic shock were reversed in seven of 15 patients on anti-lipid A compared to two of seven patients treated with placebo . In the anti-lipid A-treated group, three of 15 patients died, and in the placebo group two of seven . This difference is not statistically significant.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1987 Mar, 183(4), 337 - 57
{Bacteriological, clinical, and pharmacokinetic studies of perioperative antibiotic prophylaxis in head and neck surgery}; Borneff M et al.; The point of this study was to analyze the possible benefits of perioperative antibiotic prophylaxis in patients from whom oral cavity or throat tumors are removed . The criteria used to judge the efficacy of each treatment included the clinical course of the treatment, the bacterial colonization of the surgical area as well as the growth of bacteria during the postoperative phase . 50 patients were chosen and grouped according to their surgical treatment: laryngectomy (n = 20), partial laryngectomy (n = 22) or tongue, floor of the mouth, soft palate, gum or base of the tongue partial resection (n = 8) . Within each surgical group, patients were randomly chosen for antibiotic prophylaxis; others constituted the untreated control group . The antibiotic prophylaxis consisted of 5 g Mezlocillin administered at the time of narcosis for 20 min followed by 0.5 g Metronidazol for 10 min . These medications were given in 8-hour intervals for three days following surgery . Investigation of the first 20 patients (prophylaxis group n = 7, control group n = 13) revealed that the combination of Mezlocillin and Metronidazol positively influenced post-operative recovery (no complications) while the patients without prophylactic antibiotic treatment suffered general or local complication leading to, in 10 cases, the necessity of postoperative therapy . On the basis of these results, the random grouping of the patients was ended and all 30 remaining patients were given the antibiotic prophylaxis . Regardless of antibiotic treatment, the great majority of microbes isolated from throat swabs and tracheal secretions were gram-negative, aerobic bacteria . A prerequisite for efficacious prophylaxis is that the antibiotics be applied before the operation, so that a sufficient concentration is present at the time of pharyngotomy . On the basis of pharmacokinetic investigations, administration of the antibiotic 30 min preoperatively fulfills this requirement . Further, our recommendation, based on our measurement of the spectrum of bacteria present and their growth is that the antibiotics be applied over a period of three days postoperatively . This recommendation is also based on the fact that some patients (those having undergone partial laryngectomy or tongue, floor of the mouth, base of the tongue partial resections) have suffered loss of the swallowing reflex so that there exists a continuous contamination of the surgical area with pathogens or facultative pathogens coming from the nasal or oral cavities.

J Clin Invest, 1987 Mar, 79(3), 918 - 25
Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon; Taylor FB Jr et al.; Gram-negative septicemia elicits multiple abnormalities of the coagulation system . Although products of coagulation can lead to clot formation, thereby potentiating organ damage, recent work has shown that low concentrations of thrombin can protect animals from the shock state . Because these amounts of thrombin also lead to formation in vivo of the anticoagulant enzyme, activated protein C, we examined the role of protein C in modulation of Escherichia coli shock in baboons . First, we infused activated protein C and lethal concentrations of E . coli organisms, which prevented the coagulopathic, hepatotoxic, and lethal effects of E . coli . Second, using an antibody to protein C we blocked protein C activation in vivo to determine if this influenced the response to lethal and sublethal concentrations of E . coli organisms . Under these conditions the response to lethal concentrations of E . coli organisms was made more severe and the response to sublethal concentrations of E . coli was made lethal . The coagulopathic, hepatotoxic, and lethal responses in this latter case were prevented by infusion of exogenous protein C.

J Virol, 1987 Mar, 61(3), 812 - 8
Macrophages from endotoxin-hyporesponsive (Lpsd) C3H/HeJ mice are permissive for vesicular stomatitis virus because of reduced levels of endogenous interferon: possible mechanism for natural resistance to virus infection; Vogel SN et al.; The C3H/HeJ mouse strain bears an autosomal gene defect, Lpsd, which results in a greatly diminished capacity to respond to endotoxin, the ubiquitous lipopolysaccharide derived from the cell walls of gram-negative bacteria . These mice also exhibit greater susceptibility to a variety of viral and bacterial infections than syngeneic, fully lipopolysaccharide-responsive (Lpsn) mouse strains and possess macrophages with defects in differentiation which are reversed by treatment with exogenous interferon (IFN) . To test directly the hypothesis that C3H/HeJ macrophages are deficient in endogenous IFN levels, macrophages from C3H/HeJ (Lpsd) and C3H/OuJ (Lpsn) mice were compared for sensitivity to vesicular stomatitis virus . At a multiplicity of infection of 0.1, C3H/OuJ macrophages were completely refractory to infection, whereas C3H/HeJ macrophages were permissive for replication, and infection resulted in 100% cytopathic effect . These findings were confirmed with a second inbred Lpsn and Lpsd strain pair . Levels of 2',5'-oligoadenylate synthetase were significantly higher in Lpsn cells . C3H/HeJ macrophages, derived from bone marrow precursors under the influence of macrophage colony-stimulating factor, shown previously to induce IFN in macrophages, were as refractory as C3H/OuJ macrophages . Exposure of nonpermissive macrophages to anti-IFN-alpha/beta antibody prior to infection rendered cells permissive . Our findings suggest that endotoxin provides a primary stimulus for the maintenance of normal macrophage differentiation and innate resistance via the induction of endogenous IFN by macrophages.

Eur J Biochem, 1987 Feb 16, 163(1), 73 - 7
Nucleotide sequence of the gene for the peptidoglycan-associated lipoprotein of Escherichia coli K12; Chen R et al.; During attempts to clone the gene for the Escherichia coli outer membrane protein III another gene was recovered . Its nucleotide sequence was determined and the deduced amino acid sequence showed that the gene does not encode protein III . It codes for a 173-residue polypeptide; 21 NH2-terminal residues are typical for a signal peptide . The sequence around the putative site (Ala-Cys) for removing this peptide, Ala-Ile-Ala-Ala-Cys-Ser-Ser-Asn, is highly homologous to that of the major cell envelope lipoprotein (Braun lipoprotein) surrounding its processing site; it is also homologous to the consensus pentapeptide Leu-Leu-Ala-Gly-Cys present in other lipoproteins of gram-negative bacteria . It could be shown that the gene expresses a lipoprotein with all the properties, including the amino acid composition, of the peptidoglycan-associated lipoprotein (PAL) {Mizuno, T . (1979) J . Biochem . (Tokyo) 86, 991-1000} . Therefore, the cloned gene is the pal gene . The protein does not contain hydrophobic regions which would serve as a membrane anchor . Tandemly repeated amino acid sequences exist at and near the NH2-terminus of the mature protein which are homologous to such repeats in the Braun lipoprotein, suggesting a common origin of this part of the two proteins . Attempts to place a transposon into the pal gene were unsuccessful . Hence the complete absence of the protein may be lethal and its function remains unknown.

Arch Surg, 1987 Feb, 122(2), 207 - 12
Effect of altered volume of distribution on aminoglycoside levels in patients in surgical intensive care; Niemiec PW Jr et al.; The apparent volume of distribution (Vd) of aminoglycosides was found to be increased in 100 patients in a surgical intensive care unit who had gram-negative pneumonia or intraabdominal sepsis and acute physiologic scores greater than 12 . Following loading or maintenance doses, carefully timed blood samples were collected for measurements of serum concentrations by fluorescence polarization immunoassay . The Vd, determined by linear regression analysis of a one-compartment model using the Sawchuk-Zaske method, was 0.34 +/- 0.121 L/kg and was larger than the normal Vd of 0.20 to 0.25 L/kg, suggesting a 36% to 70% increase in extracellular fluid volume . Since there is a predictable increase in aminoglycoside Vd in the septic surgical patient, a proportionately larger aminoglycoside dosage is required initially to achieve desirable peak serum levels . Close monitoring of blood levels during maintenance dosing is suggested since dynamic changes in renal function and aminoglycoside Vd occur in the critically ill.

Blood, 1987 Feb, 69(2), 652 - 9
Cellular and subcellular localization of the bactericidal/permeability-increasing protein of neutrophils; Weiss J et al.; Human and rabbit polymorphonuclear leukocytes contain a bactericidal/permeability-increasing protein (BPI), a potent cytotoxin active specifically against gram-negative bacteria . To identify the cell population(s) producing BPI, we have examined mature and immature human blood cells for BPI by immunofluorescence of intact cells and radioimmunoassay and bioassay of cell extracts . By immunofluorescence and radioimmunoassay of cells from peripheral blood, BPI was detected only in neutrophils; immunofluorescent staining was punctate, indicative of the granule localization of BPI . Nearly all (greater than 90%) BPI was recovered during the subcellular fractionation of neutrophils (N2 cavitation and discontinuous Percoll gradient) in fractions containing primary granules . Little BPI was released from intact cells during degranulation (cytochalasin B and f-Met-Leu-Phe) or could be extracted from isolated granules with salt or weak acid, which suggests that most granule-associated BPI is membrane bound . Double staining of bone marrow smears for BPI and lactoferrin revealed BPI only in neutrophil precursors including (pro)myelocytelike cells lacking lactoferrin, a marker of neutrophil secondary granules . Of several human cell lines tested, only the promyelocytelike HL-60 (and to a lesser extent, KG-1) cells contained BPI . BPI was present in a more mature subpopulation (less than 25%) of untreated HL-60 cells, recognized by surface marker analysis (rosetting with IgG-sensitized sheep RBC, the absence of proliferation-associated cell surface antigen) . Induction of neutrophilic or monocytic differentiation caused, respectively, a small (approximately 50%) rise or fall in the BPI content . These findings indicate that BPI is a specific product of the neutrophil lineage and, hence, of the specialized cytotoxic apparatus of the neutrophil that plays an essential role in host defense v gram-negative bacteria.

Blood, 1987 Feb, 69(2), 640 - 4
Recombinant tumor necrosis factor causes activation of human granulocytes; Larrick JW et al.; We have tested the hypothesis that tumor necrosis factor (TNF), by binding to and activating granulocytes, may contribute to the pathogenesis of gram-negative sepsis and the adult respiratory distress syndrome (ARDS) . Buffy coat granulocytes incubated with as little as 0.5 ng/mL of recombinant TNF (rTNF) showed a dose-related increase in nitroblue tetrazolium dye reduction, in granulocyte polarization, in superoxide anion release, and in visually apparent aggregation . Purified lipopolysaccharide (1 microgram/mL) caused polymorphonuclear (PMN) aggregation and activation that was neutralized by polymyxin B . The release of superoxide was augmented by preincubation of the PMNs with gamma-interferon . The effect of TNF was neutralized by TNF-specific murine monoclonal antibodies but not by polymyxin B . Scatchard analysis of 125I-rTNF binding to granulocytes revealed about 1,200 receptors per cell with a Kd of 4.9 X 10(-10) mol/L . These results suggest that the release of TNF by mononuclear phagocytes contributes to granulocyte activation and aggregation during inflammation.

Antimicrob Agents Chemother, 1987 Feb, 31(2), 300 - 5
Molecular hybridization versus isoelectric focusing to determine TEM-type beta-lactamases in gram-negative bacteria; Jouvenot M et al.; Isoelectric focusing and molecular hybridization with a TEM DNA probe were used to screen for TEM beta-lactamase in 328 bacterial isolates representing 11 gram-negative genera . The TEM enzyme was detected in 50% of isolates, and nine additional types of beta-lactamase could be identified in 36.9% of isolates . The TEM gene was detected in 53.6% of isolates . The results obtained by both methods were concordant in 92.7% of the entire sample . In situ colony hybridization with a specific probe therefore appears to be a convenient method to screen rapidly for the presence of homologous genetic sequences among a large number of isolates . Positive hybridization was observed for 16 isolates in which no TEM beta-lactamase was detected by isoelectric focusing . The significance of this hybridization remains to be determined.

Environ Res, 1987 Feb, 42(1), 63 - 71
Toxicologic interactions between ozone and bacterial endotoxin; Peavy DL et al.; The effects of acute exposure of mice to bacterial lipopolysaccharide (LPS), the endotoxin of gram negative microorganisms, and ozone (O3) have been investigated . Intraperitoneal (ip) administration of 5 mg/kg LPS to CD-1 mice followed by exposure to 15 ppm O3 for 1.5 hr produced synergistic effects as measured by pulmonary edemagenesis and lethality assays . In contrast, ip administration of 0.1-1.6 mg/kg LPS to CD-1 mice over 5 consecutive days, a dose regimen resulting in LPS tolerance, protected against a lethal challenge of 20 ppm O3 for 3 hr . A statistically significant increase in catalase and glutathione peroxidase activity was measured in homogenates of lungs obtained from CD-1 mice receiving a tolerance-inducing regimen of LPS . These results demonstrate that two, distinct toxicologic interactions can occur between O3 and bacterial LPS . Synergism between these agents could explain, in part, the increased susceptibility of O3-exposed animals to respiratory infection with gram negative microorganisms . Protection resulting from LPS-induced increases in pulmonary antioxidant activity provides additional evidence that O3 and, possibly, LPS mediate their toxicity through oxidative mechanisms.

Bone Marrow Transplant, 1987 Feb, 1(3), 271 - 9
Autologous bone marrow transplantation for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia--a comparison; Anderson CC et al.; Forty-two patients with acute leukaemia were treated with autologous bone marrow transplantation (ABMT) using a combination chemotherapy protocol for bone marrow ablation . The response to high-dose chemotherapy and ABMT and its associated morbidity and mortality have been compared in 24 patients with acute myeloid leukaemia (AML) and 18 patients with acute lymphoblastic leukaemia (ALL) . In 16 patients with AML treated with ABMT during first complete remission (CR), ten patients (62.5%) remain in unmaintained remission; median follow up is 32 months . In eight patients with ALL treated in first CR, only one remains in remission 32 months post-ABMT, with three patients dying non-leukaemic deaths . Fourteen of 18 patients (AML and ALL) treated after first remission have died of recurrent leukaemia, two died non-leukaemic deaths and two remain well 31 and 55 months post-ABMT; both have ALL . The length of hospital stay and the amount of blood product support were similar in both groups . Haematological recovery post-ABMT was delayed in patients with AML compared to patients with ALL but this difference was not significant . Rapidly progressive lung infection was thought to be the cause of four early deaths (4/18) in patients with ALL but none in patients with AML . Severe gram-negative infections were significantly more common in patients with AML.

Immunol Lett, 1987 Feb, 14(3), 203 - 8
Antibody-independent killing of gram-negative bacteria via the classical pathway of complement; Loos M et al.; The experiments in this paper provided evidence that, besides lipopolysaccharides (LPS), porins of gram-negative bacteria bind to C1q and C1 . From these experiments, we concluded that the association of LPS and porins (outer membrane proteins, OMP) may potentiate the C1q and C1 binding in the absence of specific antibodies . This antibody independent binding of C1 to LPS and porins is a prerequisite for the activation of the classical pathway of complement leading to the killing of serum-sensitive bacteria.

Antimicrob Agents Chemother, 1987 Feb, 31(2), 306 - 11
Organization of two sulfonamide resistance genes on plasmids of gram-negative bacteria; Swedberg G; The organization of two widely distributed sulfonamide resistance genes has been studied . The type I gene was linked to other resistance genes, like streptomycin resistance in R100 and trimethoprim resistance in R388 and other recently isolated plasmids from Sri Lanka . In R388, the sulfonamide resistance gene was transcribed from a promoter of its own, but in all other studied plasmids the linked genes were transcribed from a common promoter . This was especially established with a clone derived from plasmid R6-5, in which transposon mutagenesis showed that expression of sulfonamide resistance was completely dependent on the linked streptomycin resistance gene . The type II sulfonamide resistance gene was independently transcribed and found on two kinds of small resistance plasmids and also on large plasmids isolated from clinical material.

J Biol Chem, 1987 Jan 25, 262(3), 1122 - 8
The biosynthesis of gram-negative endotoxin . A novel kinase in Escherichia coli membranes that incorporates the 4'-phosphate of lipid A; Ray BL et al.; Extracts of Escherichia coli contain an enzyme that generates the beta,1----6 linkage of lipid A from fatty-acylated monosaccharide precursors, according to the reaction: 2,3-diacyl-GlcN-1-P + UDP-2,3-diacyl-GlcN----2,3-diacyl-GlcN (beta, 1----6)2,3-diacyl-GlcN-1-P + UDP (Ray, B . L., Painter, G., and Raetz, C . R . H . (1984) J . Biol . Chem . 259, 4852-4859) . We now describe a membrane-bound kinase that phosphorylates the 4'-position of the above tetraacyldisaccharide 1-phosphate product . The lipid A 4'-kinase is distinct from the diglyceride kinase of E . coli . When crude membrane preparations are employed, several nucleoside triphosphates are able to support the phosphorylation of the tetraacyldisaccharide 1-phosphate, but ATP is the most efficient . The 4'-kinase requires Mg2+ and is stimulated by phospholipids, especially cardiolipin . Under optimal conditions the specific activity in crude extracts is 0.5 nmol/min/mg . The enzyme is rapidly inactivated by preincubation in the presence of detergents, such as Nonidet P-40 or octylglucoside, but phosphoenolpyruvate and glycerol stabilize the enzyme . The product generated in vitro has been characterized by fast atom bombardment mass spectrometry and by 1H and 31P NMR spectroscopy . Those analyses confirm that the 4' hydroxyl is the site of phosphorylation . The 4'-kinase reported here is likely to represent a key step in the de novo biosynthesis of lipid A.

Br Med J (Clin Res Ed), 1987 Jan 24, 294(6566), 208 - 10
Non-secretion of ABO blood group antigens as a host susceptibility factor in the spondyloarthropathies; Shinebaum R et al.; Gram negative bacteria precipitate reactive arthritis and may be concerned in the pathogenesis of ankylosing spondylitis and other spondyloarthropathies . Susceptibility to many infectious agents is associated with ABO blood group or secretor state, or both . The distribution of the ABO blood group or secretor state, or both, was therefore determined in 87 patients with ankylosing spondylitis and 32 with other forms of spondyloarthropathy . The prevalence of non-secretors was significantly increased in the total patient group (54/114; 47%) and in the subgroup with ankylosing spondylitis (41/84; 49%) compared with local controls (89/334; 27%) (p less than 0.001) . Other subgroups of patients showed a similarly increased prevalence of non-secretion (33-47%) . The distribution of ABO blood groups did not differ between patients and controls . The association between non-secretor state and ankylosing spondylitis strengthens the hypothesis that ankylosing spondylitis is a form of reactive arthritis . It also suggests several pathogenic mechanisms which may be relevant to the initial hostparasite interaction in ankylosing spondylitis.

Schweiz Med Wochenschr, 1987 Jan 17, 117(3), 84 - 90
{Indications for passive immunotherapy in infectious diseases}; Baumgartner JD; The most important indications for passive immunotherapy in the field of infectious diseases are reviewed . Intramuscular immunoglobulins are useful in prophylaxis and treatment of diseases due to bacterial exotoxins and in prophylaxis of some viral infections . However, their efficacy against bacterial infections has not been demonstrated . Intravenous immunoglobulins have theoretical advantages in these infections . The few clinical studies performed in neonates and in patients of surgical intensive care units have suggested modest benefits . However, these studies did not allow to decide whether intravenous immunoglobulins have a role in these situations . Another approach still under investigation is to administer polyclonal antibodies directed against the central part of the endotoxin, the structure of which is well preserved among gram-negative bacteria . These antibodies have improved the survival of patients with gram-negative bacteremia or septic shock . When given prophylactically, they have reduced the incidence of gram-negative shock and related mortality in patients from surgical intensive care units . Further studies are in progress to determine the class and the precise specificity of these protective antibodies.

Cell, 1987 Jan 16, 48(1), 55 - 62
Biosynthesis and structure of stable branched RNA covalently linked to the 5' end of multicopy single-stranded DNA of Stigmatella aurantiaca; Furuichi T et al.; Stigmatella aurantiaca, a gram-negative bacterium, contains approximately 500 copies per cell of a short single-stranded linear DNA (multicopy single-stranded DNA: msDNA) . This DNA is attached to a branched RNA (msdRNA) by its 5' end . The entire sequence of msdRNA was determined and found to consist of 76 bases . The msDNA is linked at the 19th G residue of msdRNA by a 2', 5' phosphodiester linkage . The coding region for msdRNA (msr) is located downstream of the coding region for msDNA (msd) . These coding regions exist in opposite orientation with respect to each other and overlap by 8 bases at their 3' ends . Biosynthesis of RNA-linked msDNA was characterized and mechanisms of synthesis are proposed.

Cell, 1987 Jan 16, 48(1), 47 - 53
Branched RNA covalently linked to the 5' end of a single-stranded DNA in Stigmatella aurantiaca: structure of msDNA; Furuichi T et al.; Stigmatella aurantiaca is a gliding, gram-negative bacterium that shows a spectacular fruiting body formation upon starvation of nutrient . This bacterium was found to contain approximately 500 copies per cell of a short single-stranded linear DNA (multicopy single-stranded DNA: msDNA) . The primary structure of msDNA was determined and found to consist of 162 or 163 deoxyribonucleotides . Its unique chromosomal gene was cloned and sequenced . The msDNA was found to be attached to a branched RNA by its 5' end . Structural analysis of the branched RNA revealed that it consists of a triribonucleotide, 5'A-G-(C or U)3', and that msDNA is branched out from the 2' position of the rG residue forming a 2', 5' phosphodiester linkage with the dC residue at the 5' end of msDNA.

Klin Wochenschr, 1987 Jan 15, 65(2), 61 - 8
The clinical significance of prostaglandins and thromboxane as mediators of septic shock; Oettinger W et al.; An evaluation was made of 106 surgical patients with Gram-negative septic shock, both for clinical criteria as well as the biochemical mediators endotoxin, prostaglandin F2 alpha, prostaglandin I2 (prostacyclin), and thromboxane . These data were correlated to various defined shock phases, functional data of vital organs, and clinical outcome . Patients underwent invasive organ function monitoring and the usual laboratory tests of intensive care . Prostaglandins and thromboxane were measured radioimmunologically, endotoxin by the limulus amebocyte lysate test . Endotoxin proved to be a more accurate predictor of severe sepsis than did positive blood cultures . Endotoxin as well as prostaglandins and thromboxane are predominantly released in early shock phases, appearing in plasma concentrations, which correlate with the severity of organ failure . Sepsis-induced respiratory failure coincides with a deterioration of pulmonary prostaglandin inactivation, which contributes to the release mechanism . High systemic prostacyclin activity benefits the patients' organ functions and clinical outcomes, while a predominance of thromboxane seems to effect the opposite . Transpulmonary-thromboxane gradients correlate significantly with pulmonary hypertension in the early phases of septic shock.

Nature, 1987 Jan 8-14, 325(7000), 179 - 80
Binding of a non-beta-lactam antibiotic to penicillin-binding proteins; Nozaki Y et al.; In the search for new beta-lactam antibiotics of natural origin, the discoveries of cephamycins and sulfazecins (monobactams) were important turning points in that they accelerated many screening efforts aimed at other new compounds . In our target-directed screening for beta-lactam antibiotics using beta-lactam hypersensitive mutants, we have examined Gram-negative bacteria isolated from natural habitats and have recently reported several types of beta-lactam antibiotics such as cephabacins and formadicins . Here we report a novel antibiotic, lactivicin, found using this system . Although lactivicin has various biological activities commonly observed in beta-lactam antibiotics, it does not possess a beta-lactam ring in its molecule, but has the unique structure of a dicyclic dipeptide.

Am J Vet Res, 1987 Jan, 48(1), 91 - 5
Experimental infection and abortion of pregnant guinea pigs with a unique spirillum-like bacterium isolated from aborted ovine fetuses; Bryner JH et al.; Study was made of the pathogenicity of a spirillum-like, anaerobic, gram-negative bacterium, originally isolated from aborted lambs, for pregnant guinea pigs . Reproducible conditions for propagation and preservation of the bacterium were determined as requisite for the preparation of cultures for animal inoculation . A preliminary experiment was done with 10 pregnant guinea pigs to test for an infective dose of organisms that would produce abortion . High-passage cultures (n = 50) were used to inoculate these guinea pigs intraperitoneally . Six of 10 guinea pigs aborted, and the organism was cultured from fetal tissues of 5 guinea pigs . Isolates from 3 of the 6 guinea pigs were propagated through 4 passages on blood agar and used to infect 3 groups, each of 5 guinea pigs . A 4th group of 5 guinea pigs was inoculated with the original culture . Three of 5 animals in the first 3 groups, which had been given the low-passage cultures from the preliminary trial, and 2 of 5 guinea pigs in the 4th group, which had been given the original culture, aborted . Antibody against the spirillum was detected in 19 of 30 inoculated guinea pigs . The major microscopic lesions were acute suppurative placentitis and splenitis . This bacterium retained pathogenic properties sufficient to cause infection, abortion, and microscopic lesions in two-thirds of the guinea pigs, in spite of high in vitro passage . The organism has unique ultrastructures, and its genus and species are yet to be determined.

J Infect Dis, 1987 Jan, 155(1), 113 - 8
Septicemic plague in New Mexico; Hull HF et al.; Eighteen of the 71 cases of plague reported in New Mexico from 1980 to 1984 were septicemic . We reviewed these cases to better describe the clinical presentation of this disorder and to identify risk factors for developing septicemic plague . The symptoms (fever, chills, malaise, headache, and gastrointestinal symptoms) and signs (tachycardia, tachypnea, and hypotension) of septicemic plague are similar to those of other forms of gram-negative septicemia . Abdominal pain was reported in nearly half of the cases, and differential white blood cell counts revealed a marked shift to the left . The risk of developing septicemic plague was higher for persons greater than 40 years of age . Because of empirical antibiotic treatment of older persons, deaths from septicemic plague occurred primarily among persons less than 30 years old . Deaths from septicemic plague could be reduced by aggressive antibiotic therapy for patients with a clinical presentation suggesting gram-negative septicemia, especially patients less than 30 years old.

Equine Vet J, 1987 Jan, 19(1), 25 - 8
Plasma endotoxin levels in horses subjected to carbohydrate induced laminitis; Sprouse RF et al.; Thirteen (65 per cent) of 20 horses subjected to carbohydrate overload developed Obel Grade 3 lameness within 56 h . Increases in plasma endotoxin from control levels of less than 0.1 ng/litre to values ranging from 2.4 to 81.53 ng/litre were measured in 11 (85 per cent) of 13 horses during the onset of Obel Grade 3 lameness . Obel Grade 3 lameness was associated with rises in plasma Gram-negative endotoxin levels in 11 (92 per cent) of 12 horses . Two peak increases separated by 16 h were verified in five (45 per cent) of 11 horses that exhibited both endotoxaemia and Obel Grade 3 lameness . The first peak occurred, on average, at 32 h and the second peak at 48 h post overload when only one peak was measured, this occurred in four horses at the average time of 24 h whereas in another three horses only a 48 h or 56 h peak was detected after carbohydrate overload.

Dev Comp Immunol, 1987 Summer, 11(3), 551 - 64
Bacterial sialic acid modulates activation of the alternative complement pathway of channel catfish (Ictalurus punctatus); Ourth DD et al.; The alternative complement pathway (ACP) provides the non-immune channel catfish (Ictalurus punctatus) with protection against many Gram-negative bacteria . Very little serum bactericidal activity (0-13%) was found against 8 fish pathogens, but a strong bactericidal response (100%) was found against 7 non-pathogens . MgEGTA chelation of catfish serum did not essentially change the bactericidal results . Catfish serum heated at 56 degrees C and serum adsorbed with zymosan had no bactericidal activity . This demonstrated that the ACP was responsible for the bactericidal response . The molecular nature of the microbial surface determines whether or not the ACP will be activated . A relative lack of surface sialic acid has been found to be important for binding complement Factor B of the ACP by susceptible microbial surfaces . This study therefore examined the 15 Gram-negative bacterial fish pathogens and non-pathogens by determining their sialic acid content and their ability to elicit a bactericidal response by the catfish ACP . It was found that there was very little bactericidal activity against the fish pathogens that contained sialic acid but a very strong bactericidal response (100%) against the non-pathogens that lacked sialic acid (p = .0043) . A relative lack of sialic acid or no sialic acid therefore correlated with a strong bactericidal response by the catfish ACP . Neuraminidase treatment of the bacterial fish pathogens to remove sialic acid greatly increased the bactericidal response against them by the catfish ACP when compared with untreated bacteria (p = .0431).

Intensive Care Med, 1987, 13(5), 347 - 51
Colonization and infection in surgical intensive care patients--a prospective study; Kerver AJ et al.; Nosocomial infections are a major problem in intensive care patients . Thirty-nine patients, requiring intensive care for 5 days or more (mean 15.8 days) were prospectively investigated, to determine the relation between colonisation and nosocomial infection . Thrice weekly, cultures from the oropharynx, respiratory and digestive tract were obtained . Colonization with aerobic gram-negative microorganisms of the oropharynx, respiratory and digestive tract significantly increased during the stay in the Intensive Care Unit . In 29 patients (74%) 78 nosocomial infections were diagnosed . The most frequent nosocomial infections were pneumonia (26 patients, 66.6%), catheter-related bacteraemia (11 patients, 28.2%), and wound infections (7 patients, 17.9%) . In 59 instances (75.6%), colonization with the same potential pathogenic microorganism preceded the nosocomial infection . The overall mortality was 25.6% (10 patients), bacteraemia with aerobic gram-negative microorganisms being the cause of death in 7 patients.

Circ Shock, 1987, 22(4), 333 - 41
Effect of fibronectin supplementation in endotoxic shock in the dog; Hauptman JG et al.; An earlier study by our group demonstrated significant amelioration of hypotension, hypoglycemia, and acidosis in dogs treated with purified human plasma fibronectin prior to induction of endotoxic shock . The present study was completed to determine whether treatment with purified human plasma fibronectin 1 hr after induction of endotoxic shock would provide similar benefits . To this end, selected hemodynamic, pulmonary, acid-base, metabolic, hematological, and serum chemistry parameters were monitored for 6 hours in two groups of anesthetized dogs in Escherichia coli endotoxic shock . One group was given an intravenous injection of purified human plasma fibronectin, and the other received an equal volume of saline 1 hr after shock induction . Between-group analysis of the data revealed no significant differences between any parameter excepting modest differences in plasma glucose, albumin, alkaline phosphatase, and BUN concentrations . However, even these differences, although statistically significant, were sporadic and unimpressive . This study suggested that treatment of dogs with fibronectin during gram-negative endotoxic shock was not efficacious.

Circ Shock, 1987, 22(4), 303 - 9
Experimental gram-negative pneumonia produces a hyperdynamic septic profile; Keenan RJ et al.; General anesthesia (GA) and extensive surgery undertaken to reproduce a hyperdynamic septic shock syndrome (HSSS) may confound the observed effects of pure HSSS . A large animal model of HSSS without GA or surgery was created in sheep following production of a Pseudomonas pneumonia by direct bronchoscopic instillation into a dependent lobe using only light ketamine anesthesia . Cardiac output rose significantly (5.05 to 6.32 L/min) while SVR {1,421.4 to 1,000.5 dynes X s X cm(-5)} and mean BP (92.5 to 82.0 mmHg) fell in the septic animals . Systemic infection was confirmed by blood culture . This model reliably produces hyperdynamic sepsis without the confounding effects of GA or extensive surgery.

Prog Clin Biol Res, 1987, 231, 405 - 16
Clinical evaluation of the plasma chromogenic Limulus assay; Dolan SA et al.; Clinical correlations of the plasma chromogenic Limulus assay were evaluated in 520 septic episodes to assess the diagnostic utility of the assay in a university hospital setting . Otherwise unselected patients undergoing blood culture were studied . An association of plasma Limulus activity with gram negative bacteremia and focal infections was found (p less than .001 and p less than .01, respectively) . There was a lesser correlation between a positive assay and the presence of major hepato-intestinal illness (p = .05) . The frequency of positive tests was similar for adult and pediatric groups . There were modest correlations of a positive assay with hypotension (p = .02) and thrombocytopenia (p = .04), but only among patients with gram negative infection . Abnormal neutrophil parameters were unassociated with positive assays in any group . The sensitivity and specificity of the test for a condition known to cause endotoxemia--either gram negative infection or major intestinal disease--were low, 21% and 93% respectively . However, the predictive value of a positive test was 79%, indicating utility for the assay.

Circ Shock, 1987, 21(1), 1 - 13
Protection against disseminated intravascular coagulation and death by antithrombin-III in the Escherichia coli endotoxemic rat; Emerson TE Jr et al.; Gram-negative septic shock remains a major clinical problem . One frequently encountered complication of sepsis is disseminated intravascular coagulation (DIC) . The present study was to determine in an Escherichia coli endotoxemia awake rat model the efficacy of antithrombin-III (AT-III) prophylaxis and to explore the role of DIC in the pathogenesis of endotoxemia . We demonstrated that DIC occurs very early, before the appearance of detectable serious abnormalities in cardiovascular, metabolic, and biochemical variables indicative of organ damage or dysfunction; AT-III prophylaxis significantly ameliorates DIC, as evidenced by completely preventing the fall in plasma fibrinogen concentration and significantly limiting the increases in prothrombin time and activated partial thromboplastin time after 4 hours of endotoxemia; and AT-III prophylaxis dramatically increases permanent survival . Results of this study suggest that AT-III prophylaxis is very protective above a threshold dosage in an endotoxemic rat model and that protection is in part due to ameliorating DIC . Our data also suggest that DIC occurs very early during endotoxemia and may in part be responsible for the pathogenesis of endotoxemia in the rat . We conclude that AT-III prophylaxis may be efficacious in conditions of impending DIC, such as gram-negative septicemia/endotoxemia.

Fed Proc, 1987 Jan, 46(1), 97 - 104
Acute inflammation in gram-negative infection: endotoxin, interleukin 1, tumor necrosis factor, and neutrophils; Movat HZ et al.; Experimental bacterial infection of the dermis induced with gram-negative microorganisms is associated with an acute inflammatory reaction, which represents the principal local defense against spread of the infection . When the inflammatory reaction is quantitated with radiolabeled cells and proteins, the kinetics resemble acute inflammation induced with other agents, such as immune complexes or chemotaxins . There is an interrelationship between the components or events of the inflammatory reaction; inasmuch as vascular injury is neutrophil-dependent, neutrophils must migrate to the site where the bacteria multiply . In neutropenic animals there is no such emigration and bacterial multiplication is not inhibited . The microorganisms shed endotoxin, which in turn induces secretion of interleukin 1 (IL 1) and probably tumor necrosis factor . Endotoxin is the most potent agent (10(-15) mol vs . 10(-12) mol of C5ades Arg) capable of inducing a neutrophil influx . Desensitization or tachyphylaxis of the tissues (probably of postcapillary venular endothelium) to IL 1 seems to control cessation of the neutrophil influx (also in vitro evidence) . Phagocytosis of the bacteria by neutrophils is associated with release of oxygen radicals and lysosomal proteases from the neutrophils . These are instrumental in eliciting microvascular injury, which is characterized by enhanced vasopermeability, hemorrhage, and thrombosis.

Lab Invest, 1987 Jan, 56(1), 49 - 59
Role for macrophage products in endotoxin-induced polymorphonuclear leukocyte accumulation during inflammation; Issekutz AC et al.; Endotoxins (lipopolysaccharide, LPS) released by Gram-negative bacteria induce acute inflammation with polymorphonuclear leukocyte (PMNL) infiltration . The mechanism of PMNL accumulation appears to be complement-independent and is not well understood . Here, we report investigation of the factors which may mediate LPS-induced PMNL accumulation in the pleural cavity and skin of rabbits . The intrapleural injection of 50 ng of Escherichia coli 0111 LPS caused the appearance in the exudate fluid of an activity which, upon intradermal injection induced PMNL accumulation in the skin, as measured by a 51Cr-labeled leukocyte assay and which was confirmed histologically . This activity preceded by 30 minutes the massive influx of PMNL into the pleural cavity . 125I-labeled LPS, gel filtration chromatography, limulus amebocyte lysate assays, and polymyxin B allowed distinction between reactions in the skin attributable to LPS and reactions due to the effect of this "PMNL infiltration-inducing activity." Pleural macrophages cultured for 3 to 6 hours with 3 to 30 ng/ml of LPS also released factors which induced PMNL infiltration into the skin . Sephadex G-100 chromatography of LPS-induced pleural exudate fluid or of supernatants from LPS-stimulated macrophage cultures yielded identical elution profiles, with one major peak of PMNL infiltration-inducing activity at an apparent molecular weight of 45,000 and a minor peak at 14,000 to 18,000 . Only the low molecular weight fraction contained interleukin 1 activity . Lipid A was required for the secretion of these factors by macrophages . The LPS shed by killed E . coli also induced macrophage production of PMNL infiltration-inducing activity . The activity was sensitive to pronase, and its production was inhibited by an inhibitor of protein synthesis (cycloheximide) . The active factors did not induce PMNL chemotaxis, aggregation, or chemiluminescence in vitro indicating that the activity was not C5a . We conclude that PMNL infiltration induced by LPS and perhaps by Gram-negative bacteria, may be mediated in part by the secretion from tissue macrophages of factors which can recruit PMNLs from the blood . The most active of these (approximately equal to 45,000 daltons) lacks interleukin-1 or PMNL chemotactic activity.

Eur J Clin Pharmacol, 1987, 33(5), 469 - 72
Oral pharmacokinetics and ascitic fluid penetration of pefloxacin in cirrhosis; Cardey J et al.; Plasma and ascitic fluid concentrations of pefloxacin in 10 cirrhotic patients and 8 healthy volunteers were determined following administration of a single oral dose of 400 mg . The mean elimination half-life was significantly increased in the patients (29.0 h) compared to in 8 healthy volunteers (12.3 h) . In patients, the total plasma clearance (2.71 vs 6.85 l/h) and volume of distribution (1.12 vs 1.67 l/kg) were decreased . Estimated by the ratio of the AUC in peritoneal fluid and plasma, ascitic fluid penetration was 68% after one oral dose, and pronounced accumulation of pefloxacin in ascites was found after repeated doses . Oral pefloxacin would seem to be a convenient and useful treatment of spontaneous, gram-negative, bacterial peritonitis in cirrhosis . However, the decreased hepatic metabolism of the drug leads to a marked accumulation in plasma and ascites after repeated doses, and a reduced dose is required in these patients.

Med Oncol Tumor Pharmacother, 1987, 4(2), 59 - 66
Iatrogenic and idiopathic acute myelogenous leukemia: a comparison of clinical features and treatment complications; Williams CK et al.; We have compared the clinical and laboratory features as well as treatment complications observed in 6 patients with iatrogenic acute myelogenous leukemia (I-AML) with those of 26 patients with idiopathic acute myelogenous leukemia (AML) . I-AML patients were significantly younger and their disease appeared less virulent on admission than in the AML patients . Following identical chemotherapy, hemorrhagic complications and the need for platelet support were found to be similar for both groups . Major infections, including systemic candidiasis and Gram-negative septicemias, occurred 3 times more frequently among I-AML than AML patients . More marked suppression and delayed regeneration of the bone marrow also occurred in I-AML patients . These observations and other factors, such as post-splenectomy state and inherent immune deficiency among surgically staged lymphoma patients as well as radiation induced immunologic impairment, may have contributed to the increased propensity to develop infection observed in this group of patients . Five of the 6 I-AML and 17 of the 26 AML patients achieved remission . We attribute the satisfactory outcome in our I-AML patients to treatment in a protective environment and availability of facilities for hematologic supportive care.

Vet Res Commun, 1987, 11(1), 65 - 75
The characteristic pattern of aspartate aminotransferase and alanine aminotransferase in the bitch with the cystic hyperplasia-pyometra complex: effect of medical or surgical treatment; de Schepper J et al.; In 75 clinically normal unspayed female control dogs between two and eleven years old the average plasma level of aspartate aminotransferase (AST) was 21.6 +/- 5.7 (+/- SD) IU/l, of alanine aminotransferase (ALT) 40.4 +/- 13.0 IU/l and of the AST/ALT ratio 0.6 +/- 0.2 . These values showed only minor changes over years . In 96 bitches with the cystic hyperplasia-pyometra complex there was a very significant increase of the AST, decrease of the ALT and increase of the AST/ALT ratio . The changes were more pronounced in 62 clinically ill bitches with typical endometritis post oestrum, in 18 dogs with gram negative organisms in the uterus and in 53 bitches with white blood cell (WBC) levels higher than 40 X 10(9)/1 . Renal failure had no influence on the specific changed values . The changed values returned either temporarily to normal after prostaglandin (PGF2 alpha)-treatment or definitely after ovariohysterectomy.

Braz J Med Biol Res, 1987, 20(6), 807 - 10
In vitro study of the antibiotic activity of diterpenes; Giesbrecht AM et al.; The antibiotic activity of 16 diterpenes and of 2 phenanthrene derivatives of diterpene origin, isolated from Brazilian plants was investigated against bacteria, yeasts, dermatophytes and aflatoxin-producing fungi . Eight of the compounds were completely inactive . None showed inhibitory activity against the Gram-negative bacteria assayed or against the Aspergillus species . The phenanthrene derivatives, chemically very similar to phytoalexins isolated from orchids, were especially active.

Adv Exp Med Biol, 1987, 216B, 901 - 9
Inter-relationship between mucosal and systemic immunity determining the balance between damage and defense in the bovine gut in response to environmental antigens; Porter P et al.; At weaning, the complex interactions of macromolecular components embracing maternally derived antibodies and antigens of microbial and dietary origin, grossly influence the immune response, directing it towards protective or damaging reactions in the intestinal mucosa . In young calves, passively acquired maternal antibody surprisingly enhances the systemic IgG1 mediated type III hypersensitivity reactions to dietary antigen . Furthermore, unresponsiveness to orally administered protein antigen in the young calf fails to develop . Additionally, antigens from gram negative bacteria can influence the development of IgE mediated hypersensitivity reactions . In the normal deleterious gut reactions to protein antigens from the lumen, IgE responses infrequently occur, and are transient . However, these can be reinforced by simultaneous challenge with protein and microbial antigen . These observations bring some new perspectives on health and nutrition of young farm animals at weaning.

Scand J Plast Reconstr Surg Hand Surg, 1987, 21(3), 281 - 2
Ceftazidime treatment in severe burns . Serious infections in patients with severe burns treated with ceftazidime; Kunst MW; In combination with active surgical and general management, ceftazidime is a useful antibiotic for the treatment of Gram negative septic complications in patients with severe burn wounds . Against S . aureus, however, ceftazidime is not the therapy of choice.

Am J Ind Med, 1987, 12(6), 687 - 97
The role of endotoxin for reactions after exposure to cotton dust; Rylander R; Gram-negative bacteria and their endotoxins are present on all parts of the cotton plant and occur in large numbers after rain or frost . Endotoxins activate pulmonary macrophages that in turn recruit neutrophils into the airways . Platelets accumulate in pulmonary capillaries . The presence of these cells allows for the initiation of acute and chronic inflammation . Dose-response relationships have been demonstrated between endotoxin and fever, chest tightness, and reduction in air flow (bronchoconstriction) in cotton workers . Limited data suggest that after cotton dust exposure, other symptoms, such as airway hyperreactivity and chronic inflammation, are also related to the endotoxin exposure . Tentative thresholds for airborne endotoxins are presented.

Infection, 1987, 15 Suppl 4, S185 - 91
{Ceftazidime with and without tobramycin versus azlocillin plus tobramycin in the therapy of bronchopulmonary infections in intensive care patients}; Kljucar S et al.; In a still ongoing open, randomized prospective trial the preliminary data of 50 intensive care patients on artificial ventilation were analysed . The evaluation included clinical and bacteriological efficacy and tolerance of ceftazidime alone or in combination with tobramycin versus azlocillin plus tobramycin . Artificially ventilated patients who had been treated in an intensive care unit for at least five days were selected to enter the study because of a high probability of colonisation with gram-negative bacteria . 16 patients were treated for bronchopulmonary infection with ceftazidime alone, and 17 each were treated with ceftazidime plus tobramycin or with azlocillin plus tobramycin . In the ceftazidime group nine patients were cured and three were improved (75% clinical success) . Of the patients treated with ceftazidime plus tobramycin, 11 were cured and one was improved (75% clinical success); one patient died from very severe multiple trauma . In the azlocillin-tobramycin group, six patients were cured and two were improved (57% clinical success) . Two patients from this group died from their underlying disease and another died from multiple organ failure due to septicemia.

Microbios, 1987, 51(207), 97 - 105
Incidence and transfer of R-plasmids at a hospital in Saudi Arabia; Skotnicki ML et al.; One hundred and fifty Gram-negative bacteria isolated from patient specimens at King Faisal Specialist Hospital were examined for their ability to transfer antibiotic resistance plasmids to a sensitive Escherichia coli recipient in conjugation and transformation experiments . Agarose gel electrophoresis was used to enumerate and size the R-plasmids found, and Southern DNA hybridization was used to assess similarities between antibiotic resistance plasmids from different bacteria and sources . Of the bacterial isolates tested 65% contained plasmids, 70% of these transferred antibiotic resistance to E . coli, and 40% transferred multiple, linked resistances on R-plasmids . DNA hybridization of these R-plasmids demonstrated widespread similarities between plasmids from different bacterial genera and from different hospital locations . In particular, a gene encoding ampicillin resistance appeared especially widespread, indicating that a transposon may be mediating transmission of this resistance.

Infection, 1987, 15 Suppl 2, S89 - 95
{Antibody to lipoid A in the treatment of septic shock}; Jaspers L et al.; The protective effect of high-titer anti-lipid A hyperimmune globulin with respect to the course of the disease and the mortality rate was studied in patients with septicemia verified by positive blood cultures . Six patients were treated with anti-lipid A in an open study . Dramatic improvement in fever curves and clinical condition in some of the patients encouraged us to start a randomized double blind study . So far, 17 patients have entered the study, 16 of whom were evaluable . Immediately after a positive blood culture was found, patients received either high doses of anti-lipid A or placebo (saline solution) on two subsequent days . Before and after each infusion blood samples were taken in order to assess serum bactericidal activity and anti-lipid A titers . Because of the still small numbers of patients the results of both studies were summarized . In all patients treated with anti-lipid A clear-cut increases in anti-lipid A titers were shown . Patients with repeated gram-negative infections showed higher median anti-lipid A titers than patients without such a history . The patients treated with anti-lipid A immune globulin ran a significantly milder course than the placebo group . The severe signs of septic shock were reversed in seven of 15 patients on anti-lipid A compared to two of seven patients treated with placebo . In the anti-lipid A-treated group, three of 15 patients died, and in the placebo group two of seven . This difference is not statistically significant.

Ann Med Interne (Paris), 1987, 138(1), 56 - 60
{Eikenella corrodens infections}; Pichereau P et al.; E . corrodens is an anaerobic facultative Gram-negative rod whose natural habitat is the oral cavity and the upper respiratory tract . This work describes four new cases of verified infections associated with this bacterium . A literature review of cases from 1975 to 1984 has been made . In this report, we discuss the pathogenicity of E . corrodens and predisposing factors for infections including underlying diseases . Successful antibiotic therapy can be achieved with benzylpenicillin or ampicillin which are the drugs of choice . E . corrodens is a slow growing bacterium of low virulence, rarely isolated in current practice because of its unusual association with conditions such as human bites, infections of the oral cavity or immuno-suppressive therapy.

Jpn J Antibiot, 1987 Jan, 40(1), 1 - 24
{A parallel comparative double blind study of cefixime with cefaclor in the treatment of acute suppurative otitis media in children}; Baba S et al.; A double blind study was carried out to compare the efficacy and safety of cefixime (CFIX), a new oral cephem with cefaclor (CCL) in the treatment of 245 children weighing 10 approximately 30 kg, with acute suppurative otitis media . The daily dosages of CFIX and CCL were 3 approximately 6 mg/kg in 2 divided portions, and 20 approximately 40 mg/kg in 3 divided portions, respectively, and the drugs were administered for 7 days . The results obtained in this study are summarized as follows . Analyzed subjects were 211 patients (CFIX group: 108 patients, CCL group: 103 patients) for clinical efficacy . Efficacy rates judged by the doctor in charge were 88.9% and 83.5% in CFIX and CCL group, respectively, without significant difference between the 2 groups . Similar results were also obtained by the committee . When clinical effects were classified by clinical isolates, the efficacy rates against monomicrobial infections with Gram-negative bacteria were judged by the doctor in charge to be 100% in the CFIX group and 84.6% in the CCL group . Thus CFIX was judged to be significantly superior to CCL (P less than 0.05) . The overall eradication rates of bacteria were 97.1% in the CFIX group and 90.3% in the CCL group . The eradication rate of CFIX was significantly superior to that of CCL (P less than 0.05) . When improvements of individual symptoms were evaluated, regarding redness of the tympanic membrane and the tympanic cavity on the 3rd day of dosing, CFIX group (improvement in 84.1% of the cases) was significantly superior (P less than 0.05) to the CCL group (67.6%) . Regarding purulent secretion on the 7th day of dosing, the CFIX group (improvement in 98.1% of the cases) was also significantly superior (P less than 0.05) to the CCL group (91.3%) . Two hundred thirty eight patients were analyzed for side effects (CFIX group: 120 patients, CCL group: 118 patients) . The incidence rates of side effects were 0.8% (1/120) in the CFIX group and 1.7% (2/118) in the CCL group, and there was no significant difference between the 2 drugs . From the above results, it is concluded that CFIX is a useful oral antibiotic in the treatment of acute suppurative otitis media in children . Furthermore, CFIX is expected to be equal or superior to CCL in clinical effects.

Crit Rev Microbiol, 1987, 14(3), 195 - 227
Control of morphogenesis in myxobacteria; Shimkets LJ; The myxobacteria are Gram-negative soil bacteria that live in large communities known as swarms . The most remarkable characteristic of myxobacteria is their ability to form fruiting bodies that have a species-specific shape and color . Fruiting body formation requires the concerted effort of hundreds of thousands of cells . Development is initiated only when two conditions are satisfied . The cells must be nutritionally deprived (environmental signal) and there must be many other cells in the vicinity (intercellular signal) . The development of one species, Myxococcus xanthus, has been studied in the most detail . M . xanthus uses amino acids as its primary carbon, nitrogen, and energy source . Starvation for a single amino acid, or for inorganic phosphate, serves as the environmental signal . A variety of intercellular signals appear to control the initiation of development and the timing of subsequent developmental events.

Crit Rev Oncol Hematol, 1987, 7(1), 89 - 113
Granulocyte transfusions in neutropenic patients; Menitove JE et al.; Patients with severe neutropenia are at increased risk for systemic infection with bacteria or fungi . This risk is in proportion to both the degree and duration of the neutropenic process . Although granulocyte transfusion as a means of augmenting host defenses would appear to be a logical therapeutic intervention in clinical contexts involving severe and prolonged neutropenia, several features of granulocyte physiology and collection complicate such considerations . These include the large numbers of granulocytes normally produced by healthy hosts, the short survival of the granulocyte in the circulation after transfusion, the relatively small number of granulocytes which can be collected using currently available pheresis techniques, problems associated with alloimmunization, and the possibility of transferring disease (CMV, toxoplasmosis, hepatitis) by means of these transfusions . In the mid-1970s, well-designed clinical studies strongly suggested that patients with documented Gram-negative sepsis or tissue infection that failed to respond to appropriate antibiotics were significantly benefited by granulocyte transfusions . With recent advances in potent, broad-spectrum antibiotic availability, some have questioned whether these observations remain valid . Several studies regarding the prophylactic use of granulocyte transfusions in patients undergoing allogeneic bone marrow transplantation and/or induction therapy for leukemia have failed to reveal therapeutic benefits and suggested the possibility of significant side effects . These studies are reviewed.

Gene, 1987, 51(2-3), 275 - 80
Vectors with restriction site banks . V . pJRD215, a wide-host-range cosmid vector with multiple cloning sites; Davison J et al.; The construction of a new wide-host-range, restriction-site bank, cosmid-cloning vehicle (pJRD215) is described . The wide-host-range properties and the ability to be transferred by conjugation, extend genetic engineering to those Gram-negative species that cannot be transformed . The vector permits the cloning of genes from Gram-negative bacteria using a complementation screening procedure in a mutant host . This procedure is simplified by the possibility of construction of a cosmid gene bank so that only a few hundred clones need to be screened . Subsequent subcloning of the gene of interest is facilitated by the presence of at least 23 unique cloning sites.

J Clin Invest, 1987 Jan, 79(1), 124 - 30
Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro; Moore KL et al.; Endotoxemia is frequently associated clinically with disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in vivo is unclear . Modulation of tissue factor (TF) and thrombomodulin (TM) expression on the endothelial surface may be relevant pathophysiologic mechanisms . Stimulation of human umbilical vein endothelial cells with endotoxin (1 microgram/ml) increased surface TF activity from 1.52 +/- 0.84 to 11.89 +/- 8.12 mU/ml-10(6) cells at 6 h (n = 11) which returned to baseline by 24 h . Repeated stimulation at 24 h resulted in renewed TF expression . Endotoxin (1 microgram/ml) also caused a decrease in TM expression to 55.0 +/- 6.4% of control levels at 24 h (n = 10) that remained depressed at 48 h . Both effects were dose and serum dependent . A temporary rise in TF expression accompanied by a sustained fall in TM expression comprise a shift in the hemostatic properties of the endothelium that would favor intravascular coagulation and may contribute to the pathogenesis of DIC in gram-negative septicemia.

Histol Histopathol, 1987 Jan, 2(1), 57 - 66
Purpura cerebri in gram-negative septicaemia . A histological and immunohistochemical study; Schwenk J et al.; Two cases with brain purpura following Gram-negative septicaemia were examined morphologically and immunohistochemically . The brain lesions, including ball and ring haemorrhages, a few days old, with some microglial cells accumulated around the older foci, were restricted to the white matter . Immunohistochemically, scanty deposits of IgG, IgA and IgM mainly in the macrophages in brain, kidneys and lungs were found, whereas staining with antibodies directed against IgE and complement (C3, C4) remained negative . In the brain, immunoglobulin deposits were located mainly in the macrophages, furthermore, in and around the walls of a few intact (non-haemorrhagic) vessels; within the perivascular haemorrhagic foci no deposits could be demonstrated . The relevance of these observations to the pathogenesis of brain purpura is discussed.

Gene, 1987, 60(2-3), 227 - 35
A 'phase-shift' fusion system for the regulation of foreign gene expression by lambda repressor in gram-negative bacteria; Davison J et al.; A 'phase-shift' translation fusion vector was constructed in which mutually compatible restriction sites BamHI, BclI and BglII are positioned in such a manner that the cut point is in a different reading frame, immediately following the ATG start codon and ribosome-binding site of the lambda cro gene . The lambda cro gene is expressed from promoter pR and controlled by a thermosensitive (cI857) lambda repressor . The usefulness of the expression vector was demonstrated using a galK gene lacking the ATG start codon and fusing this to the pR promoter and ATG start codon of the lambda cro gene, resulting in cI857-regulated expression of galactokinase . The vector is of general use for foreign gene expression in Escherichia coli when the target gene has a compatible cohesive end (5'-GATC-3') at the N terminus (provided, for example, by a BamHI linker) . The lambda cI857-pR-cro-galK cassette was cloned into pJRD215, a wide-host-range plasmid and transferred by conjugation to a variety of Gram-negative bacteria . In all cases, thermosensitive regulation of galactokinase could be demonstrated, though the levels of induction varied considerably . These results show that the powerful lambda pR promoter and the efficient lambda repressor can be used to regulate expression of foreign genes in Gram-negative organisms other than E . coli.

Dermatologica, 1987, 175 Suppl 1, 158 - 68
Characterization of apoprotein metabolism and atherogenic lipoproteins during oral isotretinoin treatment; Melnik B et al.; Apoprotein, lipoprotein and lipid parameters of 36 normolipidemic subjects (23 males, mean age 22.7 +/- 7.6 years; 13 females, mean age 26.2 +/- 9.8 years) receiving oral isotretinoin (mean daily dose 0.73 +/- 0.26 mg/kg body weight) for nodulocystic acne (n = 18), severe acne papulopustulosa (n = 15), gram-negative folliculitis (n = 2) and papulopustular rosacea (n = 1) were monitored before and during isotretinoin therapy at biweekly intervals over a period of 14.6 +/- 5.6 weeks . Pretreatment values of mean plasma triglycerides increased significantly (p less than 0.001) from 81.8 +/- 31.9 mg/dl to 112.4 +/- 38.7 mg/dl (47.4%) during isotretinoin treatment . With respect to the mean percent increase of plasma triglycerides from pretreatment levels, patients were classified as nonresponders (less than 10% triglyceride increase), responders (greater than 10% less than 50% triglyceride increase) and hyperresponders (greater than 50% triglyceride increase), revealing a distribution of 25.0, 36.1 and 38.9%, respectively . Isotretinoin treatment had no influence on the isoelectric focusing pattern of apoprotein E isoforms and C apoproteins . In particular, apoprotein C-II, the cofactor of lipoprotein lipase, was not affected . No correlation between apoprotein E phenotypes (2/3, 3/3, 3/4) and the mean plasma triglyceride increase could be demonstrated . Apoprotein B-48, a marker of chylomicrons and atherogenic chylomicron remnants, could not be detected by SDS-PAGE . On the other hand in 21.0% of patients with preexisting mean lipoprotein Lp(a) levels of 18.1 +/- 12.9 mg/dl a moderate increase of atherogenic Lp(a) to mean levels of 37.0 +/- 22.0 mg/dl was observed . Pretreatment values of very-low-density lipoprotein (VLDL) apoprotein (apo) B (7.5 +/- 2.0 mg/dl), low-density lipoprotein apo B (67.3 +/- 17.5 mg/dl) and total plasma apo B (76.6 +/- 19.0 mg/dl) increased significantly to levels of 10.3 +/- 2.4 mg/dl (p less than 0.001), 75.7 +/- 15.8 mg/dl (p less than 0.10) and 85.9 +/- 17.7 mg/dl (p less than 0.05), respectively . As lipoprotein lipase and hepatic lipase activities have been shown to be unaffected by isotretinoin treatment, our data support the hypothesis that isotretinoin induces hepatic oversecretion of VLDL, a condition resembling type IV hyperlipidemia in diabetics, familial hypertriglyceridemia of familial combined hyperlipidemia.

Biomater Artif Cells Artif Organs, 1987, 15(1), 271 - 9
Efficiency of hemosorption in treatment of patients with ulcerative colitis; Kirkin BV et al.; One hundred and seven sessions of hemosorption were performed on 77 patients with severe ulcerative colitis . Clinically, improvement was demonstrated in the reduction of the signs of intoxication in 50 to 60 per cent of patients . Combination of hemosorption and anti-inflammatory medication allowed to achieve a remission or a marked improvement determined by clinical observation or endoscopy of 39 from 52 patients with a severe, total form of the disease, whereas toxic influence of sulfasalazine was controlled and extra-intestinal complications were weakened in 8 patients from 11 . Thirteen patients were operated upon due to inefficiency of therapy . Hemosorption contributed to reduction of content of protein molecules with mean molecular weight (61 per cent), phenol (73 per cent), and endotoxin of gram-negative bacteria (50 per cent) . Dynamics of acute phase reactants and humoral immune factors testifies to a weak anti-inflammatory action of hemosorption . Reduced levels of plasma protein, albumin, potassium and cholesterol were corrected or spontaneously returned to normal.

Acta Virol, 1987 Jan, 31(1), 59 - 64
Electron microscopic analysis of in vitro interaction of Rickettsia prowazekii with guinea pig macrophages . II . Macrophages from immune animals; Popov VL et al.; Alike to macrophages from intact animals, reproduction, destruction and formation of spheroplast-like forms were observed in macrophages from immune guinea pigs 2 months post-infection (p.i.) with the virulent Breinl strain of Rickettsia prowazekii . Unlike to the former, immune macrophages revealed phagolysosomes which were larger in size and contained more rickettsiae showing morphologic signs of destruction . Spheroplast-like forms occurred more often and were more numerous than in intact animals . Structures morphologically similar to L-forms of gram-negative bacteria and that of chlamydiae were also detected . After adding immune serum, more intact rickettsiae and spheroplasts were found in phagosomes as well as more phagolysosomes contained rickettsiae and spheroplasts with morphologic signs of destruction . It is suggested that clearance of immune macrophages from rickettsiae is mediated by at least two processes: on one hand by destruction of rod-shaped rickettsiae within phagolysosomes and, on the other hand, by formation and subsequent destruction of spheroplast-like forms within vacuoles, which probably also function as phagolysosomes.

Scand J Plast Reconstr Surg Hand Surg, 1987, 21(3), 269 - 72
Selective intestinal decontamination of the digestive tract for infection prophylaxis in severely burned patients; Manson WL et al.; An oral prophylactic antibiotic regimen aiming at suppression of the gram-negative rods and yeasts of the bowel flora was utilised in 48 severely burned patients to prevent burn wound colonisation . Only 17% of the patients had an actual or potential infection . Only one Pseudomonas infection occurred . The effect of this selective gastro-intestinal decontamination is discussed.

Vox Sang, 1987, 52(4), 272 - 80
Endotoxin-polymyxin complexes in an improved enzyme-linked immunosorbent assay for IgG antibodies in blood donor sera to gram-negative endotoxin core glycolipids; Scott BB et al.; Common or cross-reactive epitopes of Gram-negative endotoxins are found in the inner-core glycolipid region of the outer membrane lipopolysaccharides (LPS) . Hydrophobic LPS from rough mutants of Gram-negative bacteria, lacking serotype polysaccharide O-antigen chains, did not bind satisfactorily to polystyrene microplates for ELISA detection of cross-reactive IgG anti-endotoxin antibodies . When these LPS molecules were reacted with the cationic polypeptide polymyxin B, complexes were formed which were stable when coated on microplates . LPS-polymyxin complexes allowed optimisation of conditions for an ELISA for IgG antibodies to the core glycolipid region of endotoxins which could be used for screening large numbers of blood donor sera.

Scand J Infect Dis, 1987, 19(2), 215 - 7
Detection of bacteremia by buffy coat smears; Ristuccia PA et al.; During a 3-month period 252 blood cultures were obtained on adult patients seen in our emergency room with fever and chills suggesting bacteremia . 62/252 blood cultures were positive by standard aerobic/anaerobic blood culture techniques . Buffy coat smears were positive in 76% of patients (47/62) when stained with the acridine orange technique and in 52% (32/62) when stained by the Gram method . Acridine orange was thus superior to the Gram stain for the detection of bacteremia (p less than 0.05) . Gram-negative organisms were present in 70% of the buffy coat preparation stain by the acridine orange method . Escherichia coli was the most common organism in buffy coat smears and subsequently identified by blood culture . We conclude that acridine orange stained buffy coat smears provide rapid detection of clinically suspected bacteremia in preselected acutely ill adult patients.

J Immunol, 1986 Dec 15, 137(12), 3921 - 7
Ganglioside expression in macrophages from endotoxin responder and nonresponder mice; Yohe HC et al.; Peritoneal macrophage ganglioside patterns and ganglioside sialic acid content were compared for two congenic strains of mice having differing responses to bacterial lipopolysaccharide . Resident macrophage ganglioside patterns from C3H/HeJ mice (endotoxin hyporesponsive) and C3H/HeN mice (endotoxin responsive) were similar . Macrophages elicited with phenol-extracted or butanol-extracted endotoxin showed distinctly more complex ganglioside patterns in C3H/HeN mice . C3H/HeJ macrophages showed distinct, but less complex changes when elicited with butanol-extracted endotoxin . As expected, there were minimal alterations induced by phenol-extracted endotoxin in the C3H/HeJ patterns . When injected with whole killed E . coli, both strains of mice exhibited complex ganglioside patterns; however, there were relative differences in the quantities of multiple gangliosides . Differences in ganglioside patterns were mirrored in the relative ratios of N-acetyl- to N-glycolylneuraminic acid . When macrophages were activated by administration of either endotoxin preparation, macrophage gangliosides from C3H/HeN mice always contained a higher proportion of N-acetylneuraminic acid compared with C3H/HeJ macrophage gangliosides . Oxidative metabolism of the macrophage populations was assessed by PMA-induced H2O2 release . This indicated that endotoxin activation produced an increase in PMA-induced H2O2 release as well as a shift of sialic acid class from the N-glycolyl type to the N-acetyl type . However, no direct correlation could be made between ganglioside composition, sialic acid content, and macrophage function . These data indicate that both ganglioside composition and sialic acid composition of macrophages are profoundly altered with endotoxin activation . The data further indicate that under conditions which C3H/HeJ mice respond to Gram-negative bacteria, their macrophage ganglioside patterns still differ from normal mice.

J Biol Chem, 1986 Dec 5, 261(34), 15831 - 5
Primary structure of CTP:CMP-3-deoxy-D-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase) from Escherichia coli; Goldman RC et al.; The gene coding for CTP:CMP-3-deoxy-D-mannooctulosonate cytidylyltransferase (CMP-KDO synthetase), kds B, was previously cloned on a 9-kilobase Pst insert of Escherichia coli DNA into pBR 322 (Goldman, R . C., and Kohlbrenner, W . E . (1985) J . Bacteriol . 163, 256-261) . Using a transposon mutagenesis approach we have now located kds B on this insert, which facilitated the isolation and sequencing of a 1.3-kilobase segment of DNA containing kds B and putative RNA polymerase and ribosome binding sites . The primary structure of CMP-KDO synthetase predicted by this nucleotide sequence was verified by amino acid composition and sequence analysis of purified CMP-KDO synthetase and cleavage fragments . Our results show that kds B consists of a 744-base open reading frame coding for a 248-amino acid peptide . The molecular weight of CMP-KDO synthetase calculated from the translated sequence is 27,486, taking into account the loss of the N-terminal methionine . These data define the transcriptional unit of kds B and its translation product in molecular terms, information prerequisite to our understanding of both the mechanism of CMP-KDO formation and the regulation of the KDO metabolic pathway in Gram-negative bacteria.

South Med J, 1986 Dec, 79(12), 1499 - 502
Gram-negative bacillary meningitis in the adult: review of 39 cases; Gower DJ et al.; From 1976 through 1984, the period covered in this report, we reviewed our total experience with gram-negative meningitis in adult patients, looking especially at how treatment and mortality had changed . Thirty-nine adults had 45 episodes of gram-negative meningitis . Twenty-five patients had had a dura-arachnoid disruption, 12 a septic episode, and two a bacterial mastoiditis . The overall mortality was 35.9% . Thirteen patients were treated with a full course of intrathecal antibiotics (five or more days) and eight patients with an abbreviated course (one or two doses) . The use of chloramphenicol was associated with poor patient outcome, a finding consistent with both experimental and clinical findings of others.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Dec, 263(1-2), 137 - 41
Borrelia burgdorferi lipopolysaccharide and its role in the pathogenesis of Lyme disease; Habicht GS et al.; Lipopolysaccharides (LPS) are a constitutive part of the outer wall of gram negative bacteria . Because many of the symptoms of Lyme disease could be explained by a spirochetal LPS we have subjected Borrelia burgdorferi to standard LPS extraction techniques which yielded a LPS which accounted for 1.5-4% of the dry weight . The LPS was very similar to classical gram negative bacterial LPS both chemically and in its biological activities which included pyrogenicity, mitogenicity for lymphocytes and the induction of Interleukin 1 production by macrophages . In addition, the LPS produced an acute inflammatory reaction when injected intradermally into rabbit skin . It could also prepare a skin site for the production of the local Shwartzman reaction . These results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro and in vivo . It is likely that this molecule plays an important role in the pathogenesis of Lyme disease.

Int J Pediatr Otorhinolaryngol, 1986 Dec, 12(2), 187 - 203
Auditory brainstem response in young burn-wound patients treated with ototoxic drugs; Hall JW 3rd et al.; Burn-wound patients often require potentially ototoxic doses of aminoglycoside drugs in the treatment of gram-negative sepsis . Cochlear hearing impairment may be an unfortunate consequence of this medical therapy . We evaluated auditory sensitivity with the auditory brainstem response (ABR) in a group of 32 children with acute, severe thermal burns ranging in age from 18 months to 17 years . The mean percent of total body surface area burns was 64% . None of the subjects had a known history of hearing deficits or aminoglycoside therapy, and all yielded a normal baseline ABR upon hospital admission . Eight of the subjects (22%) showed either an abnormal ABR, or no response, at 40 dB prior to hospital discharge . The medical treatment for this group of subjects (gentamicin, amikacin, vancomycin, amphotericin B) was compared to that of a second subgroup of 7 subjects without auditory deficit but with a statistically comparable percentage of burns . The mean dosage of vancomycin was higher for the auditory impairment group than for the unimpaired group . Prediction of ototoxicity in the acute burned patient is extremely difficult as there are numerous factors that may influence the risk of cochlear damage . We conclude, however, that the ABR can be applied in early detection of auditory deficit . Follow-up audiometric assessment is advisable since auditory deficits in this population may be delayed or progressive after discontinuance of drug therapy.

J Dairy Sci, 1986 Dec, 69(12), 3002 - 4
Quality assessment of pasteurized fluid milk as related to lipopolysaccharide content; Bishop JR et al.; A study was conducted to investigate any relationship between lipopolysaccharide (endotoxin) concentration in milk and parameters associated with the keeping quality of milk . Parameters investigated were flavor intensity, standard plate count, coliform count, psychrotrophic count, and gram-negative count . Lipopolysaccharide content was determined using the Limulus Amoebocyte Lysate assay . Pasteurized whole milk samples were obtained the day of processing in .94-L containers with samples analyzed on d 0 through 21 . Significant linear relationships were detected between lipopolysaccharide concentration and days storage at 7 degrees C, flavor intensity, and psychrotrophic count.

Antimicrob Agents Chemother, 1986 Dec, 30(6), 951 - 2
Characterization of beta-lactamases in situ on polyacrylamide gels; Sanders CC et al.; An inhibitor-based characterization system which allowed the identification of beta-lactamases after isoelectric focusing on polyacrylamide gels was developed . This system, using potassium clavulanate and oxacillin, distinguished type I chromosomally mediated enzymes from other beta-lactamases of gram-negative bacteria.

Clin Chem, 1986 Dec, 32(12), 2170 - 4
Detection of complement activation in immune complex diseases: six methods compared; Sun T et al.; We compared the performance of six complement tests: electrophoresis, immunofixation, immunoelectrophoresis, and nephelometric quantifications of C3, C4, and C3d . We used 123 blood samples from 60 control subjects and 63 patients with immune complex diseases: systemic lupus erythematosus, idiopathic thrombocytopenic purpura, rheumatoid arthritis, acquired immunodeficiency syndrome, renal diseases, vasculitis, cryoglobulinemia, Gram-negative bacteremia, Hashimoto's thyroiditis, rheumatic heart disease, malaria, and chronic active hepatitis . Immunofixation and quantification of C3d were better for detecting complement activation, their sensitivity rates (90.5% and 89.3%, respectively) being higher than those of the other tests studied . Immunofixation is a relatively simple and inexpensive test, provides good resolution of protein bands, and yields results that are easily quantified with a densitometer . Nephelometry of C3d provides more rapid and accurate quantitative results than immunofixation, but commercial reagents are not yet available . The causes of false-positive results in complement tests and the mechanisms of complement activation in AIDS are also discussed.

J Immunol, 1986 Dec 1, 137(11), 3614 - 9
Analysis of the fine specificity and cross-reactivity of monoclonal anti-lipid A antibodies; Kirkland TN et al.; We have investigated the fine specificity of anti-lipid A antibodies to identify conserved lipid A antigens . Because lipid A derived from many different Gram-negative bacteria has similar biologic activities, the conserved regions may be of particular importance for the immunostimulatory and toxic properties of lipid A . We found that five of nine antibodies bound to a wide variety of Gram-negative bacteria . All these widely cross-reactive antibodies bound to the same antigenic site within lipid A . Polymyxin B, an inhibitor of lipid A activity, bound to this site as well . The widely cross-reactive antibodies bound to native and base-hydrolyzed lipid A equally well, and also bound to the monosaccharide precursor lipid X . The less cross-reactive antibodies recognized base-hydrolyzed lipid A poorly, and did not recognize lipid X at all . Other investigators have shown that lipid X has some of the activities of lipid A in vitro and can inhibit the lethal toxicity of LPS in vivo . On the basis of this study, we suggest that lipid X contains a conserved lipid A epitope as well.

Science, 1986 Nov 7, 234(4777), 743 - 6
Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide; Jakway JP et al.; Lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, activates B lymphocytes and macrophages . Pertussis toxin, which inactivates several members of the G protein family of signaling components, including Gi and transducin, was found to inhibit the lipopolysaccharide-induced responses of the WEHI-231 B lymphoma cell line and the P388D1 macrophage cell line . These results, combined with the demonstration that lipopolysaccharide inhibits adenylate cyclase activity in P388D1 cells, strongly argues that lipopolysaccharide activation of cells is mediated by a Gi-like receptor-effector coupling protein.

Agents Actions, 1986 Nov, 19(3-4), 194 - 202
Potential therapeutic efficacy of inhibitors of human phospholipase A2 in septic shock; Vadas P et al.; Soluble phospholipase A2 has been implicated in the pathogenesis of local and systemic inflammatory reactions . Elevated levels of circulating phospholipase A2 (PLA2) correlate with the severity of circulatory collapse and pulmonary dysfunction in gram-negative septic shock . Characterization of septic shock serum PLA2 revealed a calcium-dependent enzyme with absolute 2-acyl specificity with a pH optimum of 7.5 . We tested a number of therapeutic agents for their ability to inhibit PLA2 from human septic shock serum . Chloroquine, chlorpromazine, dexamethasone base, dexamethasone sodium phosphate, indomethacin, lidocaine, oleic acid, palmitic acid, promethazine, trans-retinoic acid, rutin and dl-alpha-tocopherol were all studied over the range of 10(-2) to 10(-7) M . All agents, with the sole exception of dexamethasone base, inhibited PLA2 activity at concentrations greater than 10(-3) M . PLA2 inhibition by dexamethasone sodium phosphate was factitious, due to the formation of calcium-phosphate complexes . Of the 11 agents studied, chlorpromazine was the most effective, with an IC50 of 7.5 X 10(-5) M, a membrane concentration achievable within its therapeutic range . Inhibition was non-competitive with an apparent Ki of 5 nM . Since serum PLA2 levels correlate with mortality in both experimental endotoxemia and clinical gram-negative septic shock, and chlorpromazine was previously shown to improve survival in these conditions, we postulate that its therapeutic efficacy resides at least in part in its PLA2-inhibitory activity.

J Clin Microbiol, 1986 Nov, 24(5), 882 - 3
Rapid detection of gram-negative bacterial peritonitis by the Limulus amoebocyte lysate assay; Smalley DL et al.; The chromogenic Limulus amoebocyte lysate test effectively detected 66 (100%) culture-proven gram-negative peritonitis cases among 185 continuous ambulatory peritoneal dialysis patients with clinical evidence of infectious peritonitis.

Genetika, 1986 Nov, 22(11), 2606 - 19
{Genome organization of the plasmid of IncQ/P4 group and its vector derivatives}; Tsygankov IuD et al.; The genome organization and functioning of IncQ/P4 plasmids are reviewed . Based on these plasmids, cloning vectors have been constructed for broad host range of gram-negative bacteria . Together with one- and two-replicon vectors for cloning via insertion inactivation of markers, specialized plasmid vectors are described: cosmids, promoter-probe vectors, vectors for direct selection of recombinant molecules . Examples of using broad host range vectors for gene cloning and expression in non-enteric gram-negative bacteria are presented.

Am Surg, 1986 Nov, 52(11), 613 - 7
Effects of muramyl dipeptide and lead acetate on carbon clearance and endotoxin-induced mortality in mice; Cheadle WG et al.; Muramyl dipeptide (MDP) is a nonspecific immune adjuvant thought to affect the macrophage . MDP had been used safely without immunosuppressive or toxic side effects in our laboratory and others . Endotoxin, or lipopolysaccharide (LPS), is thought to be responsible for many of the systemic toxic effects of gram-negative infection . Lead acetate potentiates the lethal effects of endotoxin, an effect attributed to increased hepatotoxicity involving both hepatocytes and Kupffer macrophages . This study was undertaken to examine putative mechanism of action of MDP relating to the reticuloendothelial system . Endotoxin was given intraperitoneally to susceptible mice that were pretreated with MDP, lead acetate, or both, and to unmodified controls . Lead acetate significantly enhanced lethality due to LPS, but pretreatment with MDP did not alter mortality . Carbon clearance was measured in mice treated with MDP, lead, or both . There was no difference in the phagocytic index of control mice and those mice treated with lead acetate at various times prior to the injection . Carbon clearance increased significantly in mice pretreated with MDP but was unaltered by the addition of lead acetate . We conclude that if hyperphagocytosis of endotoxin occurs in MDP-pretreated mice, it does not cause additional mortality . Muramyl dipeptide appeared to be a safe reticuloendothelial stimulant that did not enhance the toxicity of lead or LPS in this experimental model.

J Clin Invest, 1986 Nov, 78(5), 1136 - 41
Human platelet aggregation is initiated by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide in vitro; Schwartz BS et al.; Platelet consumption is a prominent feature of disseminated intravascular coagulation . We investigated whether monocyte procoagulant activity (PCA) might play a role in platelet consumption associated with gram-negative septicemia . Human mononuclear cells exposed in vitro to lipopolysaccharide demonstrated parallel dose-dependent increases in PCA and ability to induce platelet aggregation . Induction of platelet aggregation required the generation of thrombin dependent on coagulation Factors VII, X, and II, and calcium . This is consistent with monocyte tissue factor initiating thrombin generation . A specific monoclonal antimonocyte antibody was used to identify monocytes via indirect immunofluorescence, and demonstrated that all monocytes were included in platelet aggregates . Mononuclear cells that did not express PCA did not induce platelet aggregation and monocytes were not surrounded by platelet clumps . These data suggest that monocytes induced to express tissue factor on their surface may be important mediators of endotoxin-induced platelet, as well as fibrinogen, consumption.

Microbiol Sci, 1986 Nov, 3(11), 334 - 9
Beta-lactam resistance mechanisms in gram-negative bacteria; Cole ST et al.; Beta-lactam antibiotics are commonly used to treat a variety of bacterial infections . Gram-negative bacteria have evolved several resistance mechanisms including altered permeability and beta-lactamase production . New trends in resistance are emerging amongst clinical isolates which may reflect the choice of beta-lactam employed.

Microbiol Sci, 1986 Nov, 3(11), 324 - 9
The fate of enteric pathogenic bacteria in estuarine and marine environments; Grimes DJ et al.; Sufficient laboratory and field data are now available to hypothesize that enteric pathogens survive for very long periods of time in sea-water . In fact, these Gram-negative bacteria probably enter into dormancy, during which they remain viable and potentially virulent, yet are non-culturable when traditional bacteriological methods are employed . Increasing use of the world's oceans-for discharge of domestic wastes may result in public health problems in the future from the allochthonous human pathogens accumulating in the marine environment at disposal sites.

J Am Vet Med Assoc, 1986 Nov 1, 189(9), 1020 - 3
Conjunctivitis, tracheitis, and pneumonia associated with herpesvirus infection in green sea turtles; Jacobson ER et al.; Fourteen juvenile (15- to 20-month-old) green sea turtles (Chelonia mydas), representative of a group of sea turtles with clinical signs of respiratory tract disease, were euthanatized and submitted for necropsy . Macroscopically, lesions included periglottal necrosis, tracheitis with intraluminal caseous and laminated necrotic debris, and severe pneumonia . Several turtles had caseous conjunctival exudate covering the eyes . Microscopically, the turtles had fibrinonecrotic inflammation around the glottal opening, tracheitis, and severe bronchopneumonia and interstitial pneumonia . In multifocal areas, periglottal and tracheal epithelial cells adjacent to areas of necrosis had hypertrophic nuclei with amphophilic intranuclear inclusions . A mixed population of primarily gram-negative microorganisms was isolated from the tracheal and glottal lesions . Attempts at viral isolation in cultures of green sea turtle kidney cells resulted in the development of cytopathic effects characterized by giant cell formation and development of intranuclear inclusions . Using electron microscopy, intranuclear viral particles (88 to 99 nm in diameter) were seen in inclusion-containing tracheal and glottal epithelial cells and infected green sea turtle kidney cells; particles were consistently seen enveloping from nuclear membranes, and mature particles (132 to 147 nm) were found in the cytoplasm . On the basis of size, conformation, location, and presence of an envelope, the particles most closely resembled those of herpes-viruses.

Science, 1986 Oct 10, 234(4773), 203 - 5
Detoxification of bacterial lipopolysaccharides (endotoxins) by a human neutrophil enzyme; Munford RS et al.; Lipopolysaccharides in the cell walls of Gram-negative bacteria elicit toxic as well as potentially beneficial inflammatory responses in animals . It is now reported that tissue toxicity caused by lipopolysaccharides is preferentially reduced by an enzymatic activity in human neutrophils . Acyloxyacyl hydrolysis removes fatty acyl chains that are linked to the hydroxyl groups of 3-hydroxytetradecanoyl residues in the bioactive lipid A moiety of the lipopolysaccharides . Maximal acyloxyacyl hydrolysis reduced lipopolysaccharide tissue toxicity, as measured in the dermal Shwartzman reaction, by a factor of 100 or more . In contrast, the ability of the deacylated lipopolysaccharides to stimulate B lymphocytes to divide was decreased only by a factor of 12 . It is suggested that during tissue invasion by Gram-negative bacteria acyloxyacyl hydrolysis may be a defense mechanism that reduces the toxicity of lipopolysaccharides while preserving some of their potentially beneficial inflammatory and immune stimuli.

Immunobiology, 1986 Oct, 173(1), 41 - 55
Lipopolysaccharides as complement inhibitors by complex formation with the purified third complement component (C3); Beuscher HU et al.; Lipopolysaccharides (LPS) from different bacteria in smooth or rough form (Y . enterocolitica, Y . pseudotuberculosis, E . coli, S . typhimurium, S . marcescens) strongly inhibited hemolytic C3 in incubation mixtures with purified C3 . LPS from a core deficient mutant was still reactive, whereas lipid A no longer affected C3 activity . The physical state of LPS was critical for its effect on C3 . Strand-like LPS structures formed by Ca++-induced aggregation of solubilized LPS, as shown by electron microscopy, demonstrated the highest reactivity with C3 . Inhibition of hemolytic C3 was found to be due to complex formation between LPS and C3 by a hydrophobic reaction . The binding capacity of 1 microgram LPS-R and LPS-S was as high as 125 ng C3 and 56 ng C3, respectively . The C3b fragment required different reaction conditions for maximal binding . The strong binding capacity of LPS for the complement component C3 raises the possibility that LPS act as inhibitors of complement by interruption of the reaction cascade at local infectious sites with gram-negative bacteria.

Acta Pathol Microbiol Immunol Scand {B}, 1986 Oct, 94(5), 357 - 63
An investigation of three commercial methods for rapid identification of non-enteric gram-negative rods . Application on Pseudomonas paucimobilis and some other Pseudomonas species; Sogaard P et al.; Three commercial systems for the identification of non-enteric gram-negative rods were compared with conventional bacteriological methods as reference . The three systems were the API 20 NE, BIO-TEST ID-Trident, and ROSCO Diagnostic Tablets . The systems were tested on a set of 47 strains from the genus Pseudomonas, with the emphasis upon the yellow-pigmented species . The overall identification accuracy was 97% with the API, 19% with the BIOTEST and 68% with the ROSCO system . The API system was thus reliable, and it presented no major practical problems . The BIOTEST system was very handy . The main reason for the low accuracy was an error in the code book . The ONPG reaction was depicted as negative in the species P . paucimobilis . A positive ONPG test is a keymark in this species and 76% of the 20 strains of P . paucimobilis included in this investigation were also found positive with the BIOTEST system . The ROSCO tablets are convenient if the result of single reactions is desired . The time consumption per strain was 5.4, 4.4, and 6.2 min for the API, BIOTEST, and ROSCO systems respectively.

Lab Anim, 1986 Oct, 20(4), 281 - 5
Naturally occurring melioidosis in a colonized rhesus monkey (Macaca mulatta); Fritz PE et al.; An aged wild-caught male rhesus monkey (Macaca mulatta), maintained in a research facility for 10 years, developed bilateral pelvic limb paralysis without other signs of disease . Unresponsive to therapy, the monkey was killed and necropsied . Chronic inflammation with osteolysis of thoracic vertebrae 10-13 was observed . Pseudomonas pseudomallei was cultured and identified from cerebrospinal fluid obtained at the site of the thoracic lesion . This Gram-negative bacterium can cause infection in animals and man and may remain latent for years before the appearance of clinical signs.

Cornell Vet, 1986 Oct, 76(4), 335 - 41
Discriminant analysis of the clinical indicants for bovine coliform mastitis; White ME et al.; We used discriminant analysis to assess the indicants most useful in predicting whether a cow had coliform bacterial mastitis . One hundred and twenty-nine mastitic cows were divided into two groups, namely those with milk cultures that yielded pure or mixed gram negative organisms, and cows with other organisms or negative culture . Of 21 indicants examined by discriminate analysis only a history of previous mastitis in the affected quarter, weakness, clear or white color of milk, swelling of the udder, water consistency of the milk, lack of previous mastitis in other quarters, lack of palpable udder abscesses, and elevated body temperature were significantly associated with coliform mastitis . Using these variables 78% of cases were correctly classified.

Mol Gen Mikrobiol Virusol, 1986 Oct, (10), 3 - 13
{Genetic regulation of plasmid transfer in gram-negative bacteria}; Pekhov AP et al.; The data are reviewed on the genetic structure and regulation of tra-genes activity controlling the conjugative transfer of F, F-like plasmids as well as the transfer of some other bacterial plasmids . The effect of the systems inhibiting the conjugational transfer (fin-systems) of F and a number of derepressed F-like plasmids has been characterized on the basis of data obtained by the authors or published data . Possible mechanisms for the systems functioning in the regulation of tra-genes activity are discussed as well as the prospects of their further study.

Am J Med Sci, 1986 Oct, 292(4), 209 - 12
Endocarditis and infections of intravascular devices due to Eikenella corrodens; Decker MD et al.; Eikenella corrodens, a microaerophilic gram-negative rod, is a normal inhabitant of human mucosal surfaces . Infections involving Eikenella have been reported with increasing frequency during the past 10 years . Despite a demonstrated ability to invade the blood stream, Eikenella has rarely been implicated in endocarditis or other vascular space infections . Two patients are reported with prolonged illness due to infection of peripheral vascular prostheses with E . corrodens and prior reports of Eikenella vascular space infections are reviewed . When Eikenella is the sole infecting organism, vascular space infections tend to be indolent . However, removal of vascular prostheses may be required for cure.

Scand J Immunol, 1986 Oct, 24(4), 413 - 20
Immune responses during human schistosomiasis mansoni . XIII . Immunological status of spleen cells from hospital patients with hepatosplenic disease; Garcia AA et al.; Splenocytes from 25 patients with severe hepatosplenic schistosomiasis mansoni were obtained after therapeutic splenectomy . Spleen cells were phenotyped and analysed for responsiveness to mitogens or heterogeneous schistosome-derived antigenic preparations (eggs, SEA; adult worms, SWAP; cercariae, CERC) in blastogenesis assays and lymphokine production systems, and were compared with peripheral blood mononuclear cells (PBMN) . Splenic lymphocytes were 55% T lymphocytes (sheep erythrocyte rosette-positive) and 37% surface immunoglobulin-positive B lymphocytes . The mean T4+:T8+ ratio of these splenocytes was 1.0 . Phytohaemagglutinin stimulated spleen cell production of the lymphokine mitogenic factor, but exposure to SEA or SWAP did not . Spleen cell and PBMN blastogenic responses to SEA and SWAP were sometimes, but not always in accord . Removal of plastic adherent cells allowed the non-adherent spleen cells of 30-40% of the patients to respond substantially more vigorously to SEA, SWAP and CERC . Spleen cells from a subgroup of 20-30% of the patients failed to respond to the schistosomal antigens regardless of removal of adherent cells . Spleen cell responses to gram-negative lipopolysaccharide peaked on day 5 or 6 of culture, and were augmented by adherent cell removal . Pokeweek mitogen-stimulated responses were optimal on day 5 of culture . Spleen cells from most severe, hepatosplenic schistosomiasis mansoni patients do not respond well to schistosomal antigens or B-cell mitogens . The splenic responses of many of these patients were elevated by the removal of adherent spleen cells.

Proc Natl Acad Sci U S A, 1986 Oct, 83(19), 7236 - 40
An essential function for acyl carrier protein in the biosynthesis of membrane-derived oligosaccharides of Escherichia coli; Therisod H et al.; Membrane-derived oligosaccharides are branched, substituted beta-glucans localized in the periplasmic space of Escherichia coli and other Gram-negative bacteria . The biosynthesis of membrane-derived oligosaccharides and of analogous periplasmic oligosaccharides found in plant bacteria is of particular interest because it is subject to strict osmotic regulation {Miller, K.J., Kennedy, E.P., and Reinhold, V.N . (1986) Science 231, 48-51} . An enzyme system catalyzing the synthesis of the (beta 1-2)-linked glucan backbone of E . coli membrane-derived oligosaccharides from UDP-glucose requires both a membrane component and a cytosolic protein termed transglucosylation factor . The factor has now been purified to apparent homogeneity and has been found to be identical to acyl carrier protein (ACP), the phosphopantetheine-containing protein of low molecular weight that has long been known to be essential for fatty acid synthesis in E . coli and other organisms . Both are small, heat-stable, highly anionic proteins with identical chromatographic and electrophoretic behavior . ACP of the highest purity has an activity in the transglucosylation system indistinguishable from that of the protein independently purified as transglucosylation factor . Antibody raised against pure ACP completely inhibits transglucosylation activity; this inhibition is overcome by titration of the antibody with either ACP or transglucosylation factor . These findings provide evidence for an essential function of ACP unrelated to the biosynthesis of lipid.

Infect Immun, 1986 Sep, 53(3), 678 - 84
Demonstration of a peptidoglycan-linked lipoprotein and characterization of its trypsin fragment in the outer membrane of Brucella spp; Gomez-Miguel MJ et al.; The sodium dodecyl sulfate (SDS) extraction-trypsin digestion protocol used by Braun and Sieglin (V . Braun and U . Sieglin, Eur . J . Biochem . 13:336-346, 1970) to show the peptidoglycan-linked lipoprotein of Escherichia coli was applied to both Brucella abortus and E . coli . Whereas a single polypeptide of 8,000 molecular weight was obtained from E . coli, several proteins of apparent molecular weight lower than 35,000 were demonstrated by SDS-polyacrylamide gel electrophoresis in B . abortus . These results did not change when the trypsin digestion conditions were modified . On the other hand, when the SDS extractions were performed under conditions more stringent than those used for other gram-negative bacteria, only a polypeptide fragment of apparent molecular weight of 8,000 was obtained from B . abortus . This polypeptide was similar to the trypsin fragment of the E . coli lipoprotein with respect to its behavior in SDS-polyacrylamide gels, isoelectric point in urea, molecular weight, and presence of both ester- and amide-linked fatty acids . Moreover, the amino acid analysis showed an overall similarity with respect to the amino acid composition of E . coli lipoprotein . A polypeptide of the same molecular weight, isoelectric point, and amino acid composition was also obtained from Brucella ovis by the same method . These results demonstrated that B . abortus and B . ovis cell envelopes contain a lipoprotein and strongly support the hypothesis that it is the only major protein covalently linked to the peptidoglycan.

J Surg Oncol, 1986 Sep, 33(1), 53 - 6
Management of acute rectal problems in leukemic patients; Boddie AW Jr et al.; In the interval 1944-1983, 54 patients with leukemia and acute rectal pathology were seen at our institution, including: 25 patients with perirectal abscesses and/or fistulas (PF/F), 16 patients with acutely prolapsed or thrombosed hemorrhoids, 11 patients with anal fissures with or without hemorrhoids, and 2 patients with perianal excoriations . In the past, concerns have been raised about development of septicemia secondary to diagnostic or therapeutic instrumentation . In only 4 of 54 cases did the clinical course clearly suggest digital examination or instrumentation of the rectum may have caused bacteremia though 13 of 54 patients had positive blood cultures for gram negative organisms at some time during their course of which 7 were clearly coliform . Most (42/54) patients were treated initially by sitz baths, suppositories, and stool softeners and/or antibiotics . We observed five patients only and treated two by radiotherapy . Eleven patients required surgical intervention for thrombosed hemorrhoids and perirectal abscess and/or fistulas . Eight other patients with PA/F drained spontaneously . Poor healing after surgical or spontaneous drainage was documented in only one case . This study suggests that sitz baths, suppositories, antibiotics, and judicious surgical drainage (where needed) form the core of therapy for these patients.

Appl Environ Microbiol, 1986 Sep, 52(3), 510 - 4
Establishment of beta-hydroxy fatty acids as chemical marker molecules for bacterial endotoxin by gas chromatography-mass spectrometry; Maitra SK et al.; Selected ion-monitoring gas chromatography-mass spectrometry was used for detection of beta-hydroxy fatty acids as an independent assay for the presence or absence of endotoxin in materials claimed to induce nonspecific activation of Limulus amoebocyte lysate . To this end, suspensions of gram-negative and -positive bacteria, one fungal species, cerebrospinal fluid, and hollow-fiber hemodialyzer rinses were assayed for endotoxin by gas chromatography-mass spectrometry and the Limulus amoebocyte lysate assay . Good qualitative agreement was shown for both methods when suspensions of test organisms were assayed . Two false-negative results were obtained by gas chromatography-mass spectrometry assays of cerebrospinal fluid and were shown to be a result of insufficient endotoxin in the cerebrospinal fluid specimens for detection by gas chromatography-mass spectrometry . Hemodialyzer rinses were Limulus assay positive; however, no beta-hydroxy fatty acids were detected by gas chromatography-mass spectrometry . These data were compared with data obtained from USP rabbit pyrogen tests of the rinse materials (nonpyrogenic) and chemical characterization of the Limulus assay-reactive rinses, which showed the rinses to be cellulosic in nature . It is suggested that beta-hydroxy fatty acids, as assayed by selected ion-monitoring gas chromatography-mass spectrometry, be used as chemical marker molecules for the presence or absence of endotoxin in materials reported to cause nonspecific activation of Limulus amoebocyte lysate.

Proc Natl Acad Sci U S A, 1986 Sep, 83(17), 6332 - 6
Nucleotide sequence of the myxobacterial hemagglutinin gene contains four homologous domains; Romeo JM et al.; Myxococcus xanthus, a Gram-negative bacterium, has a complex life cycle that includes fruiting-body formation, a primitive form of multicellular development . Myxobacterial hemagglutinin (MBHA) is a lectin that is induced during the aggregation phase of fruiting-body formation . We have cloned the gene for MBHA and determined its sequence by the dideoxy chain-termination technique . The sequence data show the probable sites for translational initiation and termination and suggest that MBHA does not contain a cleaved leader signal peptide . The DNA sequence shows four strong internal homologies . The deduced amino acid sequence shows that the protein (Mr 27,920) consists of four highly conserved domains each consisting of 67 amino acids . Thus MBHA is physically multivalent in structure, a requirement for all hemagglutinins.

Kosm Biol Aviakosm Med, 1986 Sep-Oct, 20(5), 81 - 5
{Characteristics of the formation of a microbial complex in the nutrient solutions of higher plants after the use of straw mineralization products}; Drugova NA et al.; The effect of a product of wheat straw mineralization, e . g . ecothole, on the formation of a microbial complex that is concomitant with lettuce plants during 7 vegetations (i . e . 189 days) was investigated . The plants were grown by the subirrigation-aeroponic method on nutrient solutions that were not replaced throughout the study . It was found that in the course of lettuce ontogenesis the count of microorganisms, fungi and actinomycetes varied in the range 10(5) to 10(6), 10(2) to 10(4) and 10(2) to 10(5) cells per ml solution, respectively . During all lettuce vegetations 19 bacterial species were isolated . During the first vegetation a stable microbial complex with predominant gram-negative bacteria developed . However, addition of ecothole caused an increase in the count of spore-forming bacteria, whereas in the control the count of nitrogen-fixing bacteria grew.

Pharmacol Res Commun, 1986 Aug, 18 Suppl, 181 - 96
Evidence of a role for PAF-acether in the pathophysiology of the shock state; Sanchez Crespo M et al.; The pathophysiology of the shock state includes a variety of hemodynamic changes such as systemic hypotension, pulmonary hypertension and increased vascular permeability leading to the extravasation of protein rich plasma . These changes can be initiated by different etiological factors, but many of them have been related to the stimulation of activation systems (complement, kinins, etc.) or to the generation of inflammatory mediators . The purpose of the present study has been to obtain evidence of the involvement of paf-acether in the pathogenesis of the shock state initiated in rat and mouse by Gram-negative bacteria and soluble aggregates of immunoglobulin G . The injection of 1-2 MDa aggregates of immunoglobulin G to normal Sprague-Dawley rats, induced a dose-dependent systemic hypotension which appeared about five minutes after completion of the intravenous challenge . Simultaneously, extravasation of protein-rich plasma occurred as judged from the finding of an increased clearance of 125I-BSA . In similar experiments in mice, a reduction of the vascular volume was observed using 51Cr-labelled homologous red blood cells . Under these conditions, a lipid compound analogous to paf-acether was obtained from the liver and the spleen of these animals . The generation of this compound preceded the development of blood volume depletion and could be suppressed by either quinacrine or depletion of mononuclear phagocytes by total irradiation with 700 rads . The previous treatment of the rats with the compound BN 52021 (a specific antagonist of the paf-acether receptor) at a dose of 5mg/kg, i.v., prevented the appearance of hypotension and extravasation in response to an i.v . challenge with soluble aggregates of immunoglobulin G . Interestingly, the reversal of hypotension was also observed when BN 52021 was infused after the immunoaggregates (5mg/kg) . The possible involvement of paf-acether in the hemodynamic changes of Gram-negative sepsis was studied in rats which had received an intraperitoneal inoculation of E . coli . The animals inoculated with the doses of bacteria which produced mortality showed a time- and dose-dependent increase of vascular permeability as judged from the presence of abundant peritoneal exudate and the reduction of the circulating volume . Simultaneously, significant amounts of paf-acether could be obtained from the peritoneal exudate and from the spleen preceding to the development of the circulating volume depletion.(ABSTRACT TRUNCATED AT 400 WORDS)

Jpn J Antibiot, 1986 Aug, 39(8), 2273 - 9
{A study on ceftazidime in the perinatal period}; Takase Z et al.; Ceftazidime (CAZ), a new cephem antibiotic with high activity against Gram-negative bacteria, has been investigated for use in mothers in perinatal period, and the results obtained are summarized below . Into maternal serum, umbilical cord serum and amniotic fluid, CAZ showed good transfer after intravenous administration of 1 g or 2 g into mothers, and no adverse effect appeared in their neonates . The CAZ is a very useful antibiotic for the prophylaxis and the treatment of perinatal infections at a dose level of 1-2 g per day.

J Immunol Methods, 1986 Jul 24, 91(2), 243 - 7
A rapid sensitive monoclonal assay for lipid A in solution; Gagliardi NC et al.; Lipid A is the toxic component of bacterial endotoxins (LPS) and LPS has been thought to be clinically important in Gram-negative bacterial sepsis, as well as in non-bacteremic states where endotoxemia of enteric origin may be deleterious . The presently accepted method of detecting both LPS and its common lipid A moiety is the Limulus lysate amebocyte assay (LAL), but this test cross-reacts with non-bacterial antigens and serum contains natural inhibitors to the reaction . As an extension of previous work using a polyclonal antibody, we have developed a rapid and sensitive monoclonal antibody assay for lipid A . This 3-step inhibition ELISA is reproducible in aqueous solutions and capable of detecting less than 10 pg/ml of this shared toxic endotoxin component . The assay does not detect intact LPS but acid hydrolysis releases the active lipid A for reaction . While already valuable in detecting lipid A in biological solutions, the presence of naturally occurring anti-lipid A immunoglobulins in serum interfere with the reaction and cause false positives in this inhibition assay . Clinical usefulness of the assay will depend on removal of these antibodies from serum prior to testing.

N Engl J Med, 1986 Jul 17, 315(3), 141 - 7
Autologous bone marrow transplantation in patients with acute nonlymphocytic leukemia, using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide; Yeager AM et al.; We studied 25 patients with acute nonlymphocytic leukemia in second remission (20 patients) or third remission (5 patients) in whom autologous bone marrow transplantation was performed with use of marrow incubated ex vivo with the alkylating agent 4-hydroperoxycyclophosphamide . Patients received intensive cytoreductive therapy with busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, followed by an infusion of marrow that had been collected in remission, treated with 4-hydroperoxycyclophosphamide, and cryopreserved . Four patients died from bacterial or fungal sepsis within the first month after transplantation, and one patient with persistent marrow hypoplasia died from gram-negative sepsis 155 days after infusion with autologous marrow . In the remaining patients, peripheral-blood levels of neutrophils in excess of 0.5 X 10(9) per liter and platelet counts over 50 X 10(9) per liter were attained at median intervals of 29 and 57 days after transplantation, respectively . Nine patients had leukemic relapses at 73 to 316 days (median, 182 days) after infusion of autologous marrow, for an actuarial relapse rate of 46 percent . Eleven patients (eight in second remission and three in third) remained in remission at a median of more than 400 days (range, greater than 230 to greater than 1653 days) after transplantation . The observed disease-free survival after transplantation with autologous marrow treated with 4-hydroperoxycyclophosphamide compares favorably with the results of syngeneic or allogeneic transplantation in similar groups of patients.

Am Ind Hyg Assoc J, 1986 Jul, 47(7), 421 - 6
The distribution of gram negative bacteria and endotoxin on raw cotton components; Fischer JJ et al.; The botanical composition of representative raw cottons from seven different growing regions was determined by manual removal and identification of all trash components greater than 50 micron in size . The number of gram negative bacteria (GNB) and the amount of endotoxin present in each of the separated raw cotton components were quantified . Low middling cotton contained significantly more bract-leaf trash than that found in higher quality cottons such as those in the middling grade division . Significantly more GNB and endotoxin were found in botanical trash components as well as lint of raw cotton derived from the southwest and southeast growing regions as compared to similar botanical components from far west cottons . For representative raw cottons from the 1980 USA crop we determined that 67% of the GNB and 89% of the endotoxin resided on white lint itself, from which all particulate larger than 50 micron in size had been removed manually.

Br J Haematol, 1986 Jul, 63(3), 503 - 8
Infective complications of aplastic anaemia; Keidan AJ et al.; Patients with aplastic anaemia have a relatively specific immune defect--leucopenia with neutropenia . We have carried out a retrospective analysis of infective episodes in 11 patients with aplastic anaemia . 5723 follow-up days accrued and 29 infective episodes were documented . Overall the number of infective episodes was significantly associated with the mean white cell and monocyte counts (r = 0.59, 0.02 less than P less than 0.05) but not with length of follow-up, presentation values of white cell, neutrophil and monocyte counts, or mean neutrophil count . The patients appeared to divide clinically into two groups, those at low risk (seven patients) and those high risk (four patients) of infection . Patients in the high risk group had significantly more infections (P = 0.01) and significantly lower monocyte counts (0.02 less than P less than 0.05) than patients in the low risk group . These results are in contrast to similar studies in patients with chemotherapy-induced neutropenia; in our patients the overall rate and severity of infection was low, Gram negative infections were uncommon and monocytopenia appeared to be of greater importance than neutropenia in determining susceptibility to infection.

Am Rev Respir Dis, 1986 Jul, 134(1), 170 - 1
A case of melioidosis originating in North America; Barnes PF et al.; A case of melioidosis is described in a patient from Mexico . The cases that have been previously reported to originate in the western hemisphere are critically reviewed . The clinician must be aware of this rare disease because its treatment is quite different from that of other gram-negative infections.

J Clin Invest, 1986 Jul, 78(1), 259 - 70
Gram-negative bacteremia produces both severe systolic and diastolic cardiac dysfunction in a canine model that simulates human septic shock; Natanson C et al.; A canine sepsis model that simulates the human cardiovascular response to septic shock was produced in 10 conscious unsedated dogs by implanting an Escherichia coli-infected clot into the peritoneum, resulting in bacteremia . By employing serial, simultaneous measurements of radionuclide scan-determined left ventricular (LV) ejection fraction (EF) and thermodilution cardiac index (CI), the end-diastolic volume index (EDVI) was calculated (EDVI = stroke volume index divided by EF) . By using three different methods of quantifying serial ventricular performance (EF, shifts in the Starling ventricular function curve using EDVI vs . stroke work index, and the ventricular function curve response to volume infusion), this study provides evidence (P less than 0.01) that septic shock produces a profound, but reversible, decrease in systolic ventricular performance . This decreased performance was not seen in controls and was associated with ventricular dilatation (P less than 0.01); the latter response was dependent on an adequate volume infusion . Further studies of EDVI and pulmonary capillary wedge pressure during diastole revealed a significant, though reversible, shift (P less than 0.001) in the diastolic volume/pressure (or compliance) relationship during septic shock.

Ann Intern Med, 1986 Jul, 105(1), 58 - 60
Total lymphoid irradiation in refractory systemic lupus erythematosus; Ben-Chetrit E et al.; In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects . Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro . The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis . The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy . These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.

Drug Intell Clin Pharm, 1986 Jul-Aug, 20(7-8), 562 - 7
Emergence of resistance in gram-negative bacteria: a risk of broad-spectrum beta-lactam use; Dworzack DL; A number of new beta-lactam antibiotics have been developed to overcome bacterial resistance to older agents . Such resistance usually is caused by plasmid-mediated, constituently produced beta-lactamases . Second- and third-generation cephalosporins, ureidopenicillins, acylamino penicillins, and monobactams generally are resistant to hydrolysis by these enzymes . However, inducible beta-lactamases may confer resistance to these antibiotics . This induction may occur spontaneously or in response to cefoxitin or other beta-lactam agents . The mechanisms by which inducible enzymes produce this resistance are reviewed and implications for the prophylactic and therapeutic use of newer beta-lactams are considered.

Can J Microbiol, 1986 Jul, 32(7), 607 - 10
Structure, partial elemental composition, and size of Thiopedia rosea cells and platelets; Scherrer R et al.; The phototrophic purple sulfur bacterium Thiopedia rosea forms multicellular, gas-vacuolate, regular, flat aggregates (platelets, sheets) held together by slime . Platelets found in eutrophic water consisted of slime (85% of the total wet volume) and 16 cells, while the gas-filled vacuole occupied 44% of the volume of a single wet cell . Individual platelet cells contained central spindle-shaped gas vesicles (which together constitute the cell's gas vacuole), intracytoplasmic membrane vesicles (chromatophores), and peripheral sulfur globules . Cells were surrounded by a Gram-negative type cell envelope and were connected to neighboring cells of the same platelet by mostly unstructured slime . Cells contained detectable amounts of magnesium, phosphorus, sulfur, and potassium as determined by wavelength-dispersive X-ray microanalysis . The large size and relatively low slime density of the platelet, as well as the flat shape, could greatly decrease platelet sedimentation and so stabilize the position of T . rosea within its water column.

Infect Immun, 1986 Jul, 53(1), 161 - 5
Killing of Actinobacillus actinomycetemcomitans by the human neutrophil myeloperoxidase-hydrogen peroxide-chloride system; Miyasaki KT et al.; Actinobacillus actinomycetemcomitans is a facultative gram-negative coccobacillus associated with periodontal disease and nonoral infections . This organism is resistant to serum bactericidal mechanisms but is nevertheless killed by human neutrophils under aerobic and anaerobic conditions . Most of the killing attributable to oxidative mechanisms is inhibited by sodium cyanide, which suggests that the myeloperoxidase-hydrogen peroxide-chloride (MPO-H2O2-Cl-) system may be a key factor in the oxidative killing process . In this report, we examine whether the isolated MPO-H2O2-Cl- system is bactericidal against A . actinomycetemcomitans . We found that three major chromatographic forms of MPO were capable of killing A . actinomycetemcomitans at sublethal concentrations of H2O2 and that both catalase-positive and catalase-negative strains of this organism were sensitive to killing by the MPO-H2O2-Cl- system . We conclude that the isolated MPO-H2O2-Cl- system is bactericidal for A . actinomycetemcomitans independent of other neutrophil granule constituents and may be an important component of the oxygen-dependent bactericidal activity of the neutrophil with respect to this periodontopathic organism.

Infect Immun, 1986 Jul, 53(1), 154 - 60
Oxidative and nonoxidative killing of Actinobacillus actinomycetemcomitans by human neutrophils; Miyasaki KT et al.; Actinobacillus actinomycetemcomitans is a facultative gram-negative microorganism which has been implicated as an etiologic agent in localized juvenile periodontitis and in subacute bacterial endocarditis and abscesses . Although resistant to serum bactericidal action and to oxidant injury mediated by superoxide anion (O2-) and hydrogen peroxide (H2O2), this organism is sensitive to killing by the myeloperoxidase-hydrogen peroxide-chloride system (K.T . Miyasaki, M.E . Wilson, and R.J . Genco, Infect . Immun . 53:161-165, 1986) . In this study, we examined the sensitivity of A . actinomycetemcomitans to killing by intact neutrophils under aerobic conditions, under anaerobic conditions, and under aerobic conditions in the presence of the heme-protein inhibitor sodium cyanide . Intact neutrophils killed opsonized A . actinomycetemcomitans under aerobic and anaerobic conditions, and the kinetics of these reactions indicated that both oxidative and nonoxidative mechanisms were operative . Oxidative mechanisms contributed significantly, and most of the killing attributable to oxidative mechanisms was inhibited by sodium cyanide, which suggested that the myeloperoxidase-hydrogen peroxide-chloride system participated in the oxidative process . We conclude that human neutrophils are capable of killing A . actinomycetemcomitans by both oxygen-dependent and oxygen-independent pathways, and that most oxygen-dependent killing requires myeloperoxidase activity.

Am J Med, 1986 Jun 30, 80(6B), 149 - 55
Combination therapy and monotherapy in the treatment of severe infection in the immunocompromised host; Gaya H; Profoundly granulocytopenic patients in whom fever develops are likely to have gram-negative septicemia, which may rapidly be fatal . These patients require early empiric therapy with a synergistic bactericidal combination of antibiotics that should be chosen on the basis of in vitro studies, animal models, and results of volunteer and clinical trials . From in vitro studies, it is apparent that the degree of synergy between an aminoglycoside and a beta-lactam is determined mainly by the aminoglycoside . Amikacin is the most synergistic of the aminoglycosides . A combination of an aminoglycoside such as amikacin plus a beta-lactam active against Pseudomonas is probably still the best empiric therapy available . The newer compounds and beta-lactam combinations still have to be proven effective in the clinical setting of the persistently and profoundly granulocytopenic patient with fever and bacteremia.

Am J Vet Res, 1986 Jun, 47(6), 1214 - 6
Mycoplasma bovoculi infection increases ocular colonization by Moraxella ovis in calves; Rosenbusch RF et al.; To determine whether infection with Mycoplasma bovoculi increases ocular colonization of cattle eyes with Moraxella bovis and other bacteria, colonization of ocular gram-negative bacteria were measured in eyes of cattle infected with Mycoplasma bovoculi . Strains of Moraxella ovis were chosen because these are among the most commonly isolated species of gram-negative bacteria from cattle eyes . Five strains of M ovis were characterized biochemically and by pilus structure, permitting the recognition of 2 biotypes . All strains were tested in a mouse corneal pathogenicity model . One strain of each biotype was selected for testing in calves . All 5 strains were apathogenic for mice, and the 2 strains tested in cattle did not induce keratitis . Infection of calves with Mycoplasma bovoculi increased the amount and persistence of colonization with the strains of M ovis.

Surgery, 1986 Jun, 99(6), 679 - 83
The effect of biliary obstruction on a gram-negative bacteremic challenge: a preliminary report; Scott-Conner CE et al.; Alterations in the sequestration and destruction of bacteria were studied after 10 days of biliary obstruction . Intraperitoneal injection of radiolabeled Escherichia coli was used to study bacterial localization in rats 10 days after common duct ligation and transection or sham celiotomy . Animals were sacrificed 4 hours later and uptake by liver, spleen, lung, and kidney were studied with a scintillation counter . No significant difference in localization between the two groups was noted . Bacteremia was induced in a second set of animals and quantitative bacterial organ cultures were performed . Significantly more viable organisms were identified in lung, liver, and kidney of animals that underwent common duct ligation and transection, when compared with controls that underwent sham celiotomy . This suggests that there is a defect in bacterial killing after 10 days of biliary obstruction . The inability to effectively clear and kill gram-negative bacteria in patients with biliary obstruction may account for some of the clinical complications seen in this patient population.

J Dent Res, 1986 Jun, 65(6), 913 - 7
Desulfuration of cysteine and methionine by Fusobacterium nucleatum; Pianotti R et al.; Fusobacterium nucleatum is a Gram-negative anaerobic rod-shaped bacterium frequently isolated from human dental plaque . It is capable of the desulfuration of cysteine and methionine, resulting in the formation of sulfide and thiol volatiles, respectively . Intact cells, as well as cell-free extracts produced by French pressure cell lysis of F . nucleatum, hydrolyzed radiolabeled cysteine to produce sulfide, pyruvic acid, and ammonia . The hydrolysis products of radiolabeled methionine were a volatile thiol, ketobutyrate, and ammonia . Both activities were associated with the cytoplasmic component, not the membrane . The desulfuration mechanisms are heat-labile, inhibited by the presence of excess substrate, and rates are dependent upon substrate concentration . These dissimilar pathways by F . nucleatum can account in part for the presence of sulfur-containing volatile products that occur in the mouth.

Can J Microbiol, 1986 Jun, 32(6), 447 - 64
Cadmium transport, resistance, and toxicity in bacteria, algae, and fungi; Trevors JT et al.; Cadmium is an important environmental pollutant and a potent toxicant to bacteria, algae, and fungi . Mechanisms of Cd toxicity and resistance are variable, depending on the organism . It is very clear that the form of the metal and the environment it is studied in, play an important role in how Cd exerts its effect and how the organism(s) responds . A wide range of Cd concentrations have been used to designate resistance in organisms . To date, no concentration has been specified that is applicable to all species studied under standardized conditions . Cadmium exerts its toxic effect(s) over a wide range of concentrations . In most cases, algae and cyanobacteria are the most sensitive organisms, whereas bacteria and fungi appear to be more resistant . In some bacteria, plasmid-encoded resistance can lead to reduced Cd2+ uptake . However, some Gram-negative bacteria without plasmids are just as resistant to Cd as are bacteria containing plasmids encoding for Cd resistance . According to Silver and Misra (1984), there is no evidence for enzymatic or chemical transformations associated with Cd resistance . Insufficient information is available on the genetics of Cd uptake and resistance in cyanobacteria and algae . Mechanisms remain largely unknown at this point in time . Cadmium is toxic to these organisms, causing severe inhibition of such physiological processes as growth, photosynthesis, and nitrogen fixation at concentrations less than 2 ppm, and often in the ppb range (Tables 2 and 3) . Cadmium also causes pronounced morphological aberrations in these organisms, which are probably related to deleterious effects on cell division . This may be direct or indirect, as a result of Cd effects on protein synthesis and cellular organelles such as mitochondria and chloroplasts . Cadmium is accumulated internally in algae (Table 4) as a result of a two-phase uptake process . The first phase involves a rapid physicochemical adsorption of Cd onto cell wall binding sites, which are probably proteins and (or) polysaccharides . This is followed by a lag period and then a slow, steady intracellular uptake . This latter phase is energy dependent and may involve transport systems used to accumulate other divalent cations, such as Mn2+ and Ca2+ . Some data indicate that Cd resistance, and possibly uptake, in algae and cyanobacteria is controlled by a plasmid-encoded gene(s) . Although considerable information is available on Cd toxicity to, and uptake in fungi, further work is clearly needed in several areas . There is little information about Cd uptake by filamentous fungi, and even in yeasts, information on the specificity, kinetics, and mechanisms of Cd uptake is limited.(ABSTRACT TRUNCATED AT 400 WORDS)

Am J Med, 1986 May 30, 80(5C), 101 - 11
A double beta-lactam combination versus an aminoglycoside-containing regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients; De Jongh CA et al.; The double beta-lactam combination of moxalactam plus piperacillin was compared with the aminoglycoside-containing regimen of moxalactam plus amikacin in a prospective, randomized trial of empiric therapy for 302 febrile episodes in granulocytopenic cancer patients . The moxalactam/piperacillin regimen was found to be as effective as the moxalactam/amikacin regimen (70 percent overall responses); responses with moxalactam/piperacillin and moxalactam/amikacin were similar for microbiologically documented infections (24 of 37, 65 percent, versus 20 of 35, 57 percent), for the subgroup with bacteremias (19 of 32 versus 14 of 28), and for clinically documented infections (41 of 58, 71 percent, versus 40 of 48, 83 percent) . Responses were similar also for bacteremia in patients with persistent, profound (less than 100/microliter) granulocytopenia . Among profoundly (less than 100/microliter) granulocytopenic patients with gram-negative bacteremia, an increase in the granulocyte count to more than 100/microliter during therapy and a peak bactericidal activity of 1:16 or more (the latter noted in seven of nine moxalactam/piperacillin trials and six of nine moxalactam/amikacin trials) correlated with a favorable clinical response in 85 percent (p less than or equal to 0.00003) and 92 percent (p less than or equal to 0.044), respectively . Although serious side effects were minimal with either regimen, the double beta-lactam combination was associated with significantly less frequent nephrotoxicity (two of 145 versus 12 of 130; p less than or equal to 0.003) and ototoxicity (none of 34 versus seven of 34; p less than or equal to 0.006) . The double beta-lactam combination of moxalactam plus piperacillin was found to be as effective as moxalactam plus amikacin but to have significantly less nephro- and ototoxicity.

Schweiz Med Wochenschr, 1986 May 24, 116(21), 694 - 8
{Pathomorphologic findings following intensive therapy}; Ruchti C; Based on autopsy findings in 301 adults who had died after intensive care, different patterns of single or multiple organ damage were identified . Signs of septicemia and/or exudative-to-fibrosing alveolitis (EFA) of the lungs, the prominent cause of the adult respiratory distress syndrome (ARDS), were recognized in 89 cases . Severe, progressive EFA, which appears to ensue mainly from continuing damage to alveolar walls, consequent fibroblast proliferation and so-called atelectatic induration (collapsed alveoli forming single thick septa), was registered only in individuals who had undergone long-term intensive care . The latter was necessitated in various severe conditions of which abdominal disease was the most important . Systemic disorders, such as hemorrhagic diathesis and multiple organ damage ("multiple organ failure"), showed a close correlation with septicemia . Infections with gram-negative bacteria appear to play a special role in such processes . Morphologically, these cases were characterized by multiple organ/system damage, e.g., in order of frequency, partial necrosis of renal proximal tubules, followed by signs of regeneration; jaundice; splenitis; lobular pneumonia; centrolobular-to-zonal liver necrosis, in part combined with cholestasis; petechial and/or extended hemorrhage; and others . This complex pattern contrasted strongly with findings in individuals who had been admitted to intensive care because of e.g . a cardiovascular incident: in this latter group (125 cases) intensive care was usually of short duration, progressive EFA was largely absent, signs of septicemia were exceptional, and multiple organ/system damage was rare . The group with polytraumatism (28 cases) exhibited a pattern of organ damage intermediate between (a) and (b).

J Biol Chem, 1986 May 15, 261(14), 6585 - 9
Cadaverine covalently linked to a peptidoglycan is an essential constituent of the peptidoglycan necessary for the normal growth in Selenomonas ruminantium; Kamio Y et al.; Cadaverine links covalently to the D-glutamic acid residue of the peptidoglycan in Selenomonas ruminantium, a strictly anaerobic Gram-negative bacterium (Kamio, Y., Itoh, Y., and Terawaki, Y . (1981) J . Bacteriol . 146, 49-53) . This report clarifies a physiological function of cadaverine in this organism by using DL-alpha-difluoromethyllysine, which had previously been shown to be a selective irreversible inhibitor of lysine decarboxylase of Mycoplasma dispar (Poso, H., MaCann, P.P., Tanskanen, R., Bey, P., and Sjoerdsma, A . (1984) Biochem . Biophys . Res . Commun . 125, 205-210) . DL-alpha-Difluoromethyllysine is now shown to be a potent and irreversible inhibitor of lysine decarboxylase of S . ruminantium in vitro; however, it did not inhibit the transfer of cadaverine to the alpha-carboxyl group of the D-glutamic acid residue of the peptidoglycan . DL-alpha-Difluoromethyllysine at 5 mM markedly inhibited the growth of the bacterium and caused rapid cell lysis . Immediately before the cell lysis, almost all cells became swollen, and such cells showed a loosened envelope structure when studied by electron microscopy . The peptidoglycan prepared from the DL-alpha-difluoromethyllysine-treated cells did not have covalently linked cadaverine . The growth inhibition by DL-alpha-difluoromethyllysine was completely reversed by adding cadaverine (1 mM) to the medium . Furthermore, the exogenous cadaverine was exclusively incorporated into the peptidoglycan in the presence of DL-alpha-difluoromethyllysine (5 mM), and a normal peptidoglycan was synthesized . The cell lysis and the formation of an abnormal cell structure were completely prevented by cadaverine added to the medium . We conclude that cadaverine covalently linked to the peptidoglycan in S . ruminantium is an essential constituent of the peptidoglycan and is required for cell surface integrity and the normal growth of S . ruminantium.

J Bacteriol, 1986 May, 166(2), 435 - 8
Kinetics of gram-negative bacterial cell elongation as measured by using the large rod "Lineola longa"; Baldwin WW et al.; Photomicrographic data were collected to measure the kinetics of elongation of "Lineola longa," a large gram-negative rod ranging from 5 to 10 microns long, during the exponential phase of growth . Its large size makes this organism especially well suited for light microscopic observations . Because this organism is aerobic, it was necessary to ensure a saturating supply of oxygen during growth . Oxygen was supplied by using Chlorella species, in a Wheaton microculture slide, as an oxygen donor separated from the bacteria by a thin layer of agar . In another set of experiments, water-saturated air replaced Chlorella species, with similar results . Statistical analysis of the data showed that "L . longa" elongates in an exponential manner . Minicell-like structures, small spherical cells lacking DNA, were occasionally seen to be produced by aberrant septation . These minicells were seen most often at the end of the exponential-growth phase . A model of cell growth is proposed to account for these observations.

Medicine (Baltimore), 1986 May, 65(3), 191 - 201
Hemophilus influenzae septic arthritis in adults . A report of four cases and a review of the literature; Borenstein DG et al.; The clinical and diagnostic features of 29 adult patients with H . influenzae septic arthritis are reviewed . Twelve men and 17 women ranging in age from 22 to 82 years developed the infection . H . influenzae septic arthritis is an acute, febrile disease with a mean duration of symptoms before diagnosis of 4 days . Fifteen patients had monoarticular arthritis, 6 with an infected knee . Polyarticular involvement, with a range of 2 to 9 joints, was diagnosed in 14 patients . Nineteen patients had concurrent extraarticular sites of infection, including meningitis, pneumonia, pharyngitis, sinusitis, conjunctivitis, and cellulitis . Twenty-two of 29 patients had predisposing factors for infection, including ethanolism, trauma, rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, splenectomy, multiple myeloma, lymphoma, gout, and acquired common variable hypogammaglobulinemia . Characteristic synovial fluid findings included purulent, greenish fluid, elevated WBC count, and gram-negative pleomorphic microorganisms . Treatment for these patients included antibiotic therapy, most often ampicillin and chloramphenicol, and joint drainage by repeated arthrocentesis or arthrotomy . A favorable outcome was reported in 25 of 29 patients . Hemophilus influenzae septic arthritis should be suspected in adults who are immunocompromised and have a concurrent extraarticular source of infection.

Infect Immun, 1986 Apr, 52(1), 26 - 30
Effect of methylprednisolone on bacterial clearance and endotoxin liberation during experimental sepsis induced by gram-negative bacteria; Flynn PM et al.; To determine the effect of methylprednisolone administration on the clearance of bacteremia and the release and clearance of endotoxin during antibiotic therapy of gram-negative bacterial sepsis, Escherichia coli K1 sepsis was induced in paired rabbits . Moxalactam and either methylprednisolone or placebo were administered to infected rabbits 1.5 h after intraperitoneal administration of live bacteria . Serial blood samples were obtained for quantitation of bacteremia and endotoxemia, arterial blood gases, and complete blood count . Arterial blood pressure, heart rate, and core body temperature were also monitored . There were no significant differences between the methylprednisolone-treated and placebo-treated groups in either the levels of bacteremia or endotoxemia or in the physiologic, metabolic, or hematologic parameters that were measured . We conclude that methylprednisolone administration has no acute effect on bacterial clearance or on the kinetics of endotoxin release and clearance during antibiotic therapy of gram-negative bacterial sepsis in this experimental model.

Geriatrics, 1986 Apr, 41(4), 55 - 7, 60-2, 65-6
Managing sepsis--a common cause of geriatric death; Besch CL et al.; Consider where the patient acquired the infection--in the community or the hospital . Gram-negative sepsis that develops after admission to a hospital or extended-care facility is likely to be caused by multiply-resistant organisms . Lack of fever does not reliably exclude sepsis in elderly patients . Among 27 afebrile patients found to have bacteremia-fungemia, diagnosis was made in one-third only after blood cultures were drawn, and almost one-half were already receiving antibiotics.

Neurosurgery, 1986 Apr, 18(4), 402 - 6
Treatment of cerebrospinal fluid leaks and gram-negative bacillary meningitis with large doses of intrathecal amikacin and systemic antibiotics; Gilbert VE et al.; Six patients with cerebrospinal fluid (CSF) leaks and gram-negative bacillary meningitis (GNBM) were treated with large doses of intrathecal amikacin (20 to 40 mg daily) and systemic antibiotics . Bactericidal activity was measured in the CSF of each patient, and the dose of intrathecal amikacin was increased if bactericidal activity was absent . Five of six patients had no bactericidal activity with systemic antibiotics alone and/or low dose intrathecal amikacin . All six patients were cured, and three of four patients with vertebral lesions had cessation of CSF leaks within 72 hours of the start of intrathecal amikacin . Intrathecal treatment for 7 to 10 days was adequate for five patients; the CSF of all patients was sterile within 72 hours, and all had a 90% reduction of pleocytosis in the CSF within 96 hours . One patient had radicular back pain after each intrathecal injection, but other side effects were not observed . These findings indicate that CSF leaks associated with GNBM can be effectively treated with large doses of intrathecal amikacin plus systemic antibiotics.

Chemioterapia, 1986 Apr, 5(2), 109 - 12
Effects of aztreonam and netilmicin upon alveolar macrophage function; Valerio G et al.; Both aztreonam and netilmicin showed no toxic effect on alveolar macrophage function when administered at varying concentrations . Killing ability was unchanged as well . The increase of enzyme delivery, assessed at varying concentrations, was very limited and of no relevance in the pathogenesis of possible tissue damage . It can be explained on the basis of a change in the permeability of membranes or to output during phagocytosis . In cultures containing either antibiotic under similar conditions we did not note any substantial differences . The concentrations tested can be used safely in the therapy of infections due to most gram-negative bacteria.

J Clin Microbiol . 1986 Apr;23(4):803.
Septicemia caused by the gram-negative bacterium CDC IV c-2 in an immunocompromised human; Dan M et al.; A 37-year-old man with plasma cell leukemia developed nonfatal septicemia caused by the gram-negative bacterium CDC IV c-2 . Recovery followed appropriate treatment with antibiotics . The biochemical features of this organism are reviewed.

Eur J Clin Microbiol, 1986 Apr, 5(2), 141 - 7
Complement activating and opsonic capacity of monoclonal antibodies raised against Escherichia coli O111 and its rough mutant J5; Vreede RW et al.; Six monoclonal antibodies raised against Escherichia coli O111 and against its rough mutant J5 (chemotype Rc) were studied . One IgG2A, one IgM anti-J5, and one IgG2A anti-O111 monoclonal antibody did not bind to lipopolysaccharides of the homologous strain, but cross-reacted with heterologous gram-negative rods in an enzyme-linked immunosorbent assay . These three monoclonal antibodies activated complement when incubated with homologous or heterologous strains, but were opsonic neither in the presence nor in the absence of complement . The other three monoclonal antibodies were directed against lipopolysaccharide of the homologous strain, but showed no cross-reactivity . The IgG3 and one IgM anti-J5 monoclonal antibodies activated complement and were opsonic only in the presence of complement . The IgM anti-O111 monoclonal antibody activated complement and was opsonic both in the presence and absence of complement . Thus, the outcome of the interaction between bacteria, antibodies, and complement is influenced primarily by whether antibodies are directed against lipopolysaccharides or against other cell wall components.

Chemioterapia, 1986 Apr, 5(2), 120 - 4
Microbiological perspective of ketoconazole; Strippoli V et al.; The analysis of the results obtained in our trials, which took into account different experimental conditions, suggests that ketoconazole is a very effective anti-Candida drug . In particular, ketoconazole inhibits the development of the hyphal form of C . albicans which is highly invasive . In our trials, we were also able to demonstrate that it is possible to extend ketoconazole's range of action to gram-negative bacteria, if the drug is used in appropriate pharmaceutical forms . Moreover, its in vivo efficacy against dermatophytes and ifomycetes can also be explained by its ability to concentrate in keratinized tissues . From the investigations carried out on leukocyte populations, it has also been demonstrated that ketoconazole does not negatively interfere with the cell defense mechanisms of the host . In fact, the opsonic index and intraphagocytic killing do not significantly change in the presence of ketoconazole in therapeutic doses.

J Clin Pathol, 1986 Apr, 39(4), 366 - 70
Strongyloides stercoralis hyperinfestation syndrome with Escherichia coli meningitis: report of two cases; Smallman LA et al.; Two cases of Strongyloides stercoralis hyperinfestation syndrome accompanied by Gram negative bacteraemia and meningitis were studied . Both occurred in non-immunosuppressed West Indian women.

Transplantation, 1986 Apr, 41(4), 436 - 42
Serologic methods for the early diagnosis of Pneumocystis carinii infection in renal allograft recipients; Jarowenko M et al.; Because of the nephrotoxic action of trimethoprimsulfamethoxazole (TMP-SMX) in cyclosporine (CsA)-treated patients, combined with the (CsA)-treated patients, combined with the possibility of selecting resistant gram-negative or Nocardia asteroides organisms, a monitoring tool to detect early Pneumocystis carinii (PC) infection permitting a selective treatment approach is highly desirable . A review of 401 consecutive renal transplants revealed 26 cases (18 suspected and 8 histologically proved) of PC infection in 21 cadaver and 5 living-related renal recipients . The diagnosis was confirmed in 8/18 patients who were invasively studied by open-lung biopsy (1/2), bronchoscopy with transbronchial biopsy (4/9), bronchoscopy with brushing (1/2), bronchoscopy with bronchoalveolar lavage (2/5), and transpleural needle biopsy (0/1)-yielding a confirmed incidence of 2% (8/401) . All positive invasive studies had been performed prior to or within 24 hr of the inception of TMP-SMX therapy . Nine of ten negative invasive studies were performed after more than 24 hr of treatment . The mean time from transplantation to the onset of clinical symptoms was 2.5 +/- 1.5 months . The infection rate would be 6.5%, assuming all 18 suspected cases would be PC-positive if studied pretreatment . In order to assess the efficacy of a variety of serologic methods of PC detection, qualitative counter-immunoelectrophoresis (CIE) for P carinii antigen (PC-Ag), IgG antibody reactive with PC (enzyme-linked immunosorbent assay {ELISA}), and a latex particle agglutination test (LPA) were performed on 279 sera; 85 sera from the 26 suspected or proved cases, 100 sera from normal age-matched controls, and 94 sera from 78 asymptomatic allograft recipients followed as outpatients . In the eight histologically proven cases, CIE was positive in only 3/8 and turned positive late in the clinical course . LPA was positive in all histologically proved cases; however, it was also positive in 60% of asymptomatic renal recipients . In cases that developed clinical disease, LPA increased in titer weeks to months prior to the onset of symptoms . Additionally, LPA titers decreased or stabilized during successful TMP-SMX therapy, providing an early therapeutic index . Measurement of anti-PC IgG was not useful per se, as it was elevated in both controls and documented PC infection . The combination of very low antibody titer (less than or equal to 1:16) with a positive or increasing LPA PC-Ag titer appeared to be disease-predictive.(ABSTRACT TRUNCATED AT 400 WORDS)

Ric Clin Lab, 1986 Apr-Jun, 16(2), 301 - 13
Cryoglobulins and infectious diseases; Galli M et al.; The relationship between infectious diseases due to various pathogenetic factors and cryoglobulin production mechanisms has been investigated . Cryoglobulins have been evidenced in infections caused by very heterogeneous pathogens, i.e . leptospirosis, psittacosis, Mediterranean tick typhus, brucellosis, gram-negative bacterial septicemias, in which they had never been previously reported . In type A hepatitis a high cryoglobulin prevalence (91%) has been confirmed during the acute phase, with a rapid decrease both in prevalence and concentration in the subsequent stages of the disease . Cryoglobulins were all of type III and were mainly represented by IgM; anti-HAV-IgM antibodies have been evidenced in all but one cryoprecipitates . In non-A, non-B hepatitis a lower cryoglobulin prevalence (44.7%) was shown during the acute phase and the same fast decrease has been noted in the subsequent stages . Cryoglobulins were all of type III and in some cases polyclonal IgG was the only Ig class present in cryoprecipitates . The cryoglobulin prevalence in the acute phase of HBsAg-positive hepatitis amounted to 73.4%; all the cryoprecipitates were of type III . No correlation between the presence of cryoglobulins and HBeAg positivity or between cryoglobulins and delta agent infections was found . In all the cases studied the presence of cryoglobulins was related to the persistence of liver damage . Cryoglobulins were not found in HBsAg chronic carriers, while they have been evidenced, by a preliminary study, in 41.6% of HTLV-III antibody-positive subjects complaining of a persistent generalized lymphadenopathy without clinical or laboratory signs of liver impairment . No HTLV-III antibodies were found by ELISA method in the type III cryoprecipitates.

J Bacteriol, 1986 Apr, 166(1), 78 - 82
Organization of the genes for protein synthesis elongation factors Tu and G in the cyanobacterium Anacystis nidulans; Mickel FS et al.; The genes for protein synthesis elongation factors Tu and G were cloned from the cyanobacterium Anacystis nidulans . The locations of these genes were mapped within the cloned DNA fragment by hybridization with Escherichia coli probes . The organization of the cloned fragment and the DNA flanking it in the A . nidulans chromosome was also determined . The elongation factor Tu and G genes are adjacent to one another and in the same 5'-to-3' orientation . In contrast to other gram-negative bacteria, A . nidulans contains only one gene for elongation factor Tu.

Am J Surg Pathol, 1986 Apr, 10(4), 276 - 81
Cat scratch disease . Identification of bacteria in seven cases of lymphadenitis; Miller-Catchpole R et al.; A retrospective study of lymph node biopsy specimens from nine patients with the clinical findings and histologic features of cat scratch disease was undertaken to determine whether the recent report by Wear et al . that pleomorphic bacteria are present in the lymph nodes of cat scratch disease could be confirmed . In seven of our nine cases, pleomorphic bacteria were demonstrated with the Warthin-Starry (WS) silver stain . These were gram-negative with the Brown-Hopps tissue Gram stain and were almost at the limit of microscopic resolution . Lymph node specimens from 13 additional patients with nonspecific lymphadenitis who had neither clinical nor histologic findings of cat scratch disease were studied similarly; in none of these were bacteria demonstrated with the WS silver stain . After examining the distribution of the organisms and the related morphologic features in cat scratch disease, we conclude that demonstration of pleomorphic, gram-negative, WS-positive bacteria in the appropriate clinical and histologic setting can firmly establish the diagnosis of cat scratch disease.

Biochemistry, 1986 Mar 11, 25(5), 1094 - 100
Complement-mediated killing of Escherichia coli: dissipation of membrane potential by a C9-derived peptide; Dankert JR et al.; The molecular mechanism of complement-mediated killing of Gram-negative bacteria has yet to be resolved, but it is generally accepted that assembly of the membrane attack complex (MAC) of complement on the outer bacterial membrane is a required step . We have now investigated the effect of the MAC and its precursor complex, C5b-8, on the membrane potential (delta Em) across the inner bacterial membrane . Delta Em of whole cells was measured directly by using a lipophilic cation (tetraphenylphosphonium) that equilibrates with the potential or indirectly by measuring transport of solutes (proline and galactoside), which is dependent on delta Em . Our results indicate that the C5b-8 complex caused a transient collapse of delta Em in the absence of cell killing . Addition of C9 to allow formation of the MAC dissipated delta Em irreversibly, and the cells were killed . Since delta Em is generated across the inner membrane in Gram-negative bacteria, inner membrane vesicles were prepared and membrane potentials were generated either by adding D-lactate to energize the electron-transport chain or by creating a K+ diffusion potential with valinomycin . C9 added in the absence of earlier acting complement proteins had no effect on delta Em of isolated, actively respiring vesicles or on K+ diffusion potentials . In contrast, its C-terminal thrombin fragment (C9b), which has been shown earlier to contain the membrane-active domain of C9, efficiently collapsed delta Em in such vesicles . C9b did not require a specific receptor since it was effective on "right-side-out" and "inside-out" vesicles . These results are interpreted to indicate that a C9-derived fragment deenergizes cells and may be the causative agent for cell death.

Am J Med, 1986 Mar, 80(3), 369 - 76
Intracranial pressure monitors . Epidemiologic study of risk factors and infections; Aucoin PJ et al.; An increase in the number of cases of gram-negative ventriculomeningitis in patients followed with intracranial pressure monitors when compared with patients with craniotomy alone was revealed by routine surveillance data . A study was undertaken at four area institutions to describe the infections, risk factors, and management . Two hundred fifty-five patients with diagnoses of intracerebral hemorrhage (n = 86), closed trauma (n = 66), open trauma (n = 21), tumor (n = 66), and miscellaneous other conditions were compared with their nonmonitored counterparts for type of intracranial pressure monitor used, use of drains, prophylactic antibiotics, and steroids, and remote presence of infection . The presence of intracranial pressure monitor with craniotomy was associated with an 11 percent infection rate whereas craniotomy alone demonstrated a 6 percent rate . Of the intracranial pressure monitors used, the subarachnoid screw was associated with the lowest infection rate (7.5 percent) followed by the subdural cup catheter (14.9 percent) and the ventriculostomy catheter (21.9 percent) . Regardless of the monitor used, infection was twice as likely to develop in patients with open trauma or hemorrhage . The use of bacitracin flush solutions for maintenance of lumen patency was more often associated with infections . Use of prophylactic antibiotics did not significantly influence outcome.

Jpn J Antibiot, 1986 Mar, 39(3), 807 - 14
{Clinical evaluation of ceftizoxime intravenous administration in severe infections associated with hematologic disorders . Niigata Infection Study Group}; Moriyama Y et al.; Seventy-one patients with severe infections associated with hematologic disorders including leukemia, lymphoma and aplastic anemia were treated with ceftizoxime (CZX) in daily doses of 4-6 g for an average of 20.1 days . Infections associated with hematologic disorders consisted of sepsis and pneumonia, and most of the causative organisms appeared to be Gram-negative bacteria . Of the 64 patients who completed the trial, excellent response was observed in 16 and moderate response in 26 . The rate of clinical effectiveness was 65.6% . Side effects observed during the treatment included skin rash in only 1 patient, and hepatic disorders in 6 patients . However, the relationship between CZX and these abnormal findings was not established . These results indicate that CZX is a therapeutically effective and safe antibiotic for the treatment of severe infections associated with hematologic disorders.

Int J Lepr Other Mycobact Dis, 1986 Mar, 54(1), 63 - 70
Immunity to leprosy . III . The in vitro induction of B lymphocyte proliferation by mycobacteria; Douglas-Jones AG et al.; The development of murine proliferative response assays has been initiated to begin to evaluate T-lymphocyte responses to the antigens of Mycobacterium leprae . In this study, M . leprae and 13 related strains of mycobacteria have been tested for stimulatory effects in proliferation assays using murine spleen, thymus or lymph node cultures . A number of mycobacteria were found to directly stimulate the proliferation of spleen and lymph node cells of all mouse strains tested including C3H/HeJ mice . Thymocyte cultures showed no response . The mitogenic effects of mycobacteria in spleen cultures were not dependent upon the presence of T cells or adherent cells, and resulted in the production of antibody-forming cells . Thus, these bacteria acted as polyclonal B-cell mitogens and could be readily distinguished from the lipopolysaccharide of Gram-negative bacteria by their mitogenic activity on C3H/HeJ spleen cells . The species of mycobacteria which exhibit direct mitogenic effects in spleen and lymph node cultures are a particular problem when specific immune responses to the antigens of these bacteria are compared . Such comparisons are necessary if in vitro assays are to be used to determine the nature of crossreactive antigens between M . leprae and other mycobacteria.

J Clin Microbiol, 1986 Mar, 23(3), 481 - 4
Evaluation of the Gen-Probe DNA probe for the detection of legionellae in culture; Edelstein PH; A commercial DNA probe kit designed to detect rRNA from legionellae was evaluated for its ability to correctly discriminate between legionellae and non-legionellae taken from culture plates . The probe kit, made by the Gen-Probe Corp . (San Diego, Calif.), was radiolabeled with 125I, and probe bacterial RNA hybridization, detected in a simple one-tube system hybridization assay, was quantitated with a gamma counter . A total of 156 Legionella sp . strains were tested, of which 125 were Legionella pneumophila and the remainder were strains from 21 other Legionella spp . A total of 106 gram-negative non-legionellae, isolated from human respiratory tract (81%) and other body site (19%) specimens, were also tested; 14 genera and 28 species were represented . The probe easily distinguished all of the legionellae from the non-legionellae . The average legionellae/non-legionellae hybridization ratio was 42:1, and the lowest ratio was 2:1; a minor modification in the procedure increased the lowest ratio to 5:1 . In addition to correctly identifying all Legionella species, the probe was able to separate some of the various species of Legionella . L . pneumophila strains hybridized more completely to the probe than did the other Legionella spp.; L . wadsworthii and L . oakridgensis hybridized only about 25% of the probe relative to L . pneumophila . Some strains of phenotypically identified L . pneumophila had much lower hybridization to the probe than other members of the species and may represent a new Legionella species . The simplicity of the technique and specificity of the probe make it a good candidate for confirming the identity of legionellae in culture.

J Immunol, 1986 Feb 15, 136(4), 1366 - 72
Regulation of the synthesis of the third component of complement and factor B in cord blood monocytes by lipopolysaccharide; Sutton MB et al.; We compared the regulation of C3 and factor B synthesis in cord blood and adult monocytes by using techniques for identification and quantification of newly synthesized proteins, lipopolysaccharide (LPS) from several Gram-negative organisms, and precursors of LPS . Synthesis of C3 and factor B in cord blood monocytes was unaffected by lipid A (the active moiety of LPS extracted by the Westphal procedure) . In contrast, adult monocytes increased C3 synthesis by 11.5-fold and factor B synthesis by 3.1-fold in response to LPS . This difference in cord blood monocyte response to LPS was specific in that other LPS-induced monocyte functions (superoxide production and phagocytosis) were stimulated comparably in both cord blood and adult monocytes by LPS . To characterize further this regulatory difference, the roles of LPS precursors, arachidonic acid metabolites, and of factor(s) released by adult monocytes were examined . Precursors of the lipid portion of LPS (lipid X and lipid Y), LPS isolated by trichloroacetic acid extraction, and endotoxin-associated protein (EAP) increased C3 and factor B synthesis in cord blood monocytes . Inhibitors of the lipoxygenase pathway (dexamethasone, ETYA) but not of the cyclooxygenase pathway (indomethacin) abrogated the response of adult monocytes to lipid A and EAP and of cord blood monocytes to EAP . Finally, co-incubation of adult monocytes and cord blood monocytes in LPS-containing medium resulted in enhancement of C3 and factor B synthesis in cord blood monocytes . These data suggest that the difference in LPS response between cord blood and adult monocytes may result from differences in lipid processing or protein recognition of LPS, differences in the production of lipoxygenase pathway products, and/or one or more regulatory factors . The availability of human mononuclear phagocytes which exhibit distinct differences in biosynthetic responsiveness to LPS should permit investigation of the molecular mechanism(s) by which LPS affects C3 and factor B gene expression.

Res Commun Chem Pathol Pharmacol, 1986 Feb, 51(2), 221 - 30
Impaired antibiotic entry into lung tissue following acid injury; Carrillo EH et al.; The purpose of this study was to compare the lung tissue burden of intravenous (i.v.) and intrabronchial (i.b.) cefazolin, using a standardized hydrochloric acid injury to the lungs . Ten mongrel dogs were anesthetized with pentobarbital and artificially ventilated . Following administration of cefazolin i.v . (N = 5) or i.b . (N = 5), lung biopsies were obtained at 6 hourly intervals . Simultaneous serum levels were also determined . The effective time (Teff) was defined as the period during which all serum and lung specimens demonstrated antibiotic activity exceeding 8 mcg/gm . These levels should provide comprehensive coverage of common lung and wound pathogens that are sensitive to cefazolin . Teff for the i.v . group was 1 hour, while aerosolized cefazolin never produced lung levels exceeding 8 mcg/gm . Thus, these findings suggest an explanation for cefazolin failure in gram negative pneumonia.

Antimicrob Agents Chemother, 1986 Feb, 29(2), 359 - 61
Aztreonam treatment of gram-negative septicemia; Pierard D et al.; Seventy-five aztreonam treatment courses in 74 patients with gram-negative septicemia resulted in 56 clinical cures (75%), 12 partial clinical cures (16%), and 7 clinical failures (9%) . Eradication of the original pathogen from the blood was obtained in all patients but two, who had relapses 1 and 4 days, respectively, after treatment . In nine patients (12%) a superinfection was reported . Significant adverse reactions were limited to one transient urticarial rash . Aztreonam may prove to be an effective alternative for the treatment of gram-negative septicemia, but superinfections should be carefully monitored.

Methods Find Exp Clin Pharmacol, 1986 Feb, 8(2), 63 - 5
Deacylation of bacterial endotoxins by neutrophils and macrophages: early observations and hypotheses; Munford RS; Gram-negative bacterial lipopolysaccharides (LPS) are thought to play a role in immunomodulation by providing signals to cells such as macrophages, lymphocytes and neutrophils . Recent structure-activity studies indicate that many of the bioactivities of lipid A, the bioactive region of LPS, can be produced by a lipid A precursor . The precursor is a glucosamine disaccharide that is phosphorylated at 1 and 4' and that has 3-hydroxytetradecanoate residues linked to the glucosamine backbone at 2, 3, 2', and 3' . In contrast, certain toxic activities (pyrogenicity, complement activation and the ability to produce the Shwartzman reaction) appear to require complete lipid A, which additionally has nonhydroxylated fatty acids substituted to the hydroxyl groups of some of the 3-hydroxytetradecanoate residues . Earlier studies have identified enzymes (acyloxyacyl hydrolases) in neutrophils and macrophages that remove the nonhydroxylated fatty acids from complete lipid A, thus converting the lipid A to a precursor-like structure . Based on the structure-activity studies described above, it is speculated that acyloxyacyl hydrolysis reduces the toxicity of lipid A . It is also possible that enzymatic removal of the nonhydroxylated fatty acids is required for some of the stimulatory activities of lipid A.

J Antimicrob Chemother, 1986 Feb, 17(2), 215 - 9
Pharmacokinetics of aztreonam in infected patients; Mattie H et al.; Pharmacokinetic parameters of aztreonam were determined in 22 patients with severe Gram-negative infections, treated with 0.5 or 1 g tid as an infusion of 30 min duration . Plasma concentrations were determined microbiologically . Most patients had various degrees of renal impairment and they showed a wide variety of age and body weight . The mean calculated volume of distribution was 17.31 or 260 ml/kg . The total plasma clearance correlated well with the creatinine clearance; the mean plasma clearance was 82 ml/min and the extrapolated extrarenal clearance was 9 ml/min . Actually measured half lives of aztreonam varied between 1 h 20 min, in a patient with normal renal function, and 9 h 40 min in a patient with severely impaired renal function . The results differ from predictions by other authors . Based on our results a dosage adjustment schedule for renal impairment is suggested.

Biotechnol Appl Biochem, 1986 Feb, 8(1), 5 - 22
Endotoxin detection and elimination in biotechnology; Sharma SK; Endotoxins liberated by gram-negative bacteria are frequent contaminants of aqueous and physiological solutions . Because of their potent biological effects in vivo and in vitro, their detection and removal are essential for the safe parenteral administration of products produced from natural sources, as well as those produced by recombinant DNA technology . Traditional methods of endotoxin detection include the U.S . Pharmacopeia rabbit test and the Limulus amebocyte lysate test . Elimination of endotoxins, however, continues to be a problem . Standard methods of sterilization, such as autoclaving or sterile filtration, have little effect on endotoxin levels . Various techniques for the prevention of endotoxin contamination and endotoxin removal have been discussed . The overall role of endotoxin prevention, detection, and elimination in biotechnology is emphasized.

Am J Surg, 1986 Feb, 151(2), 306 - 13
Third generation cephalosporin antibiotics in surgical practice; Fry DE; The new third generation cephalosporins have a significantly greater spectrum of action against gram-negative bacteria likely to be encountered in surgical infections . This expanded spectrum may permit these drugs to be used in place of combination therapy in patients with polymicrobial infections; however, current evidence does not indicate superior results with these agents over earlier generation choices for surgical prophylaxis . The toxicity profile of these drugs warrants close monitoring for serious complications.

Biochem Int, 1986 Feb, 12(2), 207 - 14
Characterization of beta-lactamase from Mycobacterium butyricum ATCC 19979; Choubey D et al.; beta-lactamase has been purified to a homogeneous state from Mycobacterium butyricum ATCC 19979 . The molecular weight (Mr = 29,000) and the isoelectric point (4,0) of the enzyme have been determined . The enzyme showed both penicillinase and cephalosporinase activity, but had relatively more of the former . With respect to substrate-profile the enzyme resembled the plasmid specified TEM-type beta-lactamases commonly encountered in Gram-negative bacteria . The enzyme was insensitive to p-chloromercuribenzoate, sodium chloride, or iodine inhibition.

Acta Chir Scand, 1986 Feb, 152, 135 - 8
Vasoactive intestinal polypeptide and somatostatin in experimental endogenous gram-negative peritonitis; Almdahl SM et al.; Vasoactive intestinal polypeptide (VIP) and somatostatin were measured during endogenous gram-negative peritonitis and septicaemia in rats . Both peptides were found to increase in blood, but not in peritoneal fluid . The VIP values coincided with the levels of endotoxin and bacterial counts . However, if the development of profound shock was prevented by intravenous fluid supply, scarcely any changes in plasma VIP or somatostatin were found . Somatostatin is known to inhibit VIP . Our findings suggested breakdown of this regulatory inhibition in lethal gram-negative sepsis . They also supported the concept that specific release of the peptides takes place, not merely passive diffusion from injured cells.

Infect Immun, 1986 Feb, 51(2), 586 - 93
Purification and subunit heterogeneity of pili of Bordetella bronchiseptica; Lee SW et al.; Pili were isolated and purified from Bordetella bronchiseptica . Electron microscopic observations revealed that pili are ubiquitous in this species . The occurrence of pili and flagella appeared to correlate with growth phase and colonial morphology . Pili were about 3 to 4 nm in diameter and morphologically similar to pili isolated from other gram-negative bacteria . Internal core structure was not evident . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified pili showed that up to three different pilus subunit variants could be observed on a single strain, depending on the colonial phase and culture condition . Enzyme immunoassay and immunoblot, however, showed that these subunit variants are serologically related . Mice vaccinated with purified pili were protected against a virulent intraperitoneal challenge of B . bronchiseptica . B . bronchiseptica pili were also found to be similar to Bordetella pertussis pili in morphology and in the molecular size and antigenic structure of pilus subunits . The intact pili of B . bronchiseptica and B . pertussis, however, appeared to have weak serological cross-reactivity.

J Chromatogr, 1986 Jan 10, 374(1), 27 - 35
Gas chromatographic determination of the fatty acid composition of endotoxins from different bacteria; Morris NM et al.; Endotoxins from four bacterial species extracted by three different procedures were acid-methanolyzed and the methyl esters of the fatty acids were analyzed by packed-column gas chromatography . There were qualitative and quantitative differences in the fatty acid profiles of the lipopolysaccharides isolated from four Gram-negative bacteria . Our data show considerable lot-to-lot variations in amounts of four methyl esters from the same bacterial serotype extracted by the same procedure and in the same bacterial serotype extracted by different procedures . These results indicate that extraction and perhaps culture conditions, as well as bacterial species, affect the fatty acid composition of endotoxins, hydrolyzed and derivatized by these procedures.

Toxicon, 1986, 24(1), 101 - 3
Decrease by naloxone of some electrocardiographic and biochemical changes following endotoxin induced shock in rats; Tariq M et al.; Administration of endotoxin, a lipopolysaccharide extracted from cell walls of gram negative bacteria, elicited alterations in various metabolic parameters and in the electrocardiogram of rats . Cardiac glycogen and serum glucose were decreased, while serum pyruvate and acid phosphatase levels were increased . There was initial tachycardia followed by significant bradycardia and elevation of the ST segment in the animals with shock . Erythrocyte count, haemoglobin and haematocrit were not changed after shock . Treatment with naloxone caused significant decreases in the metabolic and electrocardiographic changes induced by endotoxin.

J Antimicrob Chemother, 1986 Jan, 17(1), 115 - 20
Clinical use and toxicity of high-dose tobramycin in patients with pseudomonal endocarditis; Rybak MJ et al.; The effects and toxicity of tobramycin were assessed in 26 patients receiving high-dose (approximately 8 mg/kg/d) therapy for pseudomonal endocarditis or conventional-dose (approximately 3 mg/kg/d) therapy for various systemic Gram-negative infections . Patients in the high-dose group received an average of 29.5 g of drug over 49 days and the dosage was adjusted to maintain peak serum concentrations of 15-20 mg/l . In the conventional-dose group, patients received an average of 8.6 g of tobramycin over 26.7 days and the dosage was adjusted to achieve peak concentrations of 4-10 mg/l . Clinical evidence of acute renal failure was not apparent in any patient . Five of seven patients in the high-dose group, for whom audiologic data was available, exhibited loss of hearing sensitivity in the high frequency range, but no patients sustained significant reduction in hearing in the conversational frequency range . Patients receiving high-dose tobramycin do not appear to be at greater risk for development of nephrotoxicity than do patients receiving conventional-dose therapy.

Fed Proc, 1986 Jan, 45(1), 25 - 9
Adult respiratory distress syndrome: causes, morbidity, and mortality; Hyers TM et al.; The increased microvascular permeability of the adult respiratory distress syndrome (ARDS) results in multiple organ injury with the lungs and subsequently the kidneys as the principal targets . Direct pulmonary injury, for example aspiration of gastric contents, and indirect injury, for instance abdominal sepsis, can lead to the syndrome . The predominant infectious cause of the syndrome is gram-negative aerobic rods . Even in patients with noninfectious causes of the syndrome, the incidence of subsequent pneumonia and sepsis with gram-negative aerobic rods is high so that these organisms contribute greatly to the morbidity and mortality that result from the syndrome . Activation of polymorphonuclear leukocytes and platelets and proteolysis of complement and coagulation components contribute to the pathogenesis of the syndrome, particularly from the indirect or blood-borne causes . Therapy is largely supportive and has not progressed substantially since the introduction of positive end expiratory pressure with mechanical ventilation . The outlook for recovery of lung function of survivors is generally good, but only one in three with the syndrome survives . Because of the inflammatory properties of the syndrome, current interest for therapy centers on parenteral use of nonsteroidal antiinflammatory agents and prostaglandins of the E and I series.

Ther Drug Monit, 1986, 8(4), 440 - 5
Netilmicin in gram-negative sepsis: comparative abilities of a dosage nomogram and clinical microbiologists to predict the preferred individual dose; Batra HK et al.; The preferred dose of netilmicin was determined in each of 39 patients with severe gram-negative sepsis treated at two centres . The dose was based upon the attainment of recommended serum concentrations . Patient age varied from 18 to 87 years (mean 58), estimated creatinine clearance from 20 to 150 ml/min (mean 71), and the preferred dose from 100 to 750 mg/24 h . The dose generated by a nomogram for netilmicin was compared in retrospect with the initial dose assigned to each patient by the clinical microbiologist concerned . With respect to the preferred dose, the nomogram underdosed, on the average, by 40 mg/24 h, and the microbiologists, by 30 mg/24 h . The correlation with the preferred dose was stronger for the nomogram dose (r = 0.66; p less than 0.001, 37 df) than for the microbiologists' dose (r = 0.47; p less than 0.005, 37 df) but there was no significant difference between the two in the frequency with which they predicted the preferred dose to within 50 mg/24 h (nomogram 19/39; microbiologists 16/39) . The prescription of a fixed dose of 450 mg/day to all patients would have had a similar success rate (15/39) . The performance of the nomogram was better in patients with serum creatinine concentrations of greater than or equal to 100 microM (r = 0.82; p less than 0.001, 13 df; 10/15 within 50 mg/24 h of preferred dose) than in those with creatinine concentrations less than 100 microM (r = 0.55; p less than 0.01, 22 df; 9/24 within 50 mg/24 h of preferred dose).

Scand J Infect Dis, 1986, 18(6), 547 - 50
Carcinoembryonic antigen (CEA) in blood in cases of pneumonia; Weber TH et al.; Serum levels of carcinoembryonic antigen (CEA) were analysed in patients with pneumonia of different etiology . Significant (p less than 0.01) increases in blood CEA levels occurred in all groups of pneumonia of bacterial etiology, i.e., pneumococcal, gram-negative or chlamydial . In viral pneumonia similar increases were observed, but the changes were not statistically significant, probably due to the small number of patients . In pneumonia of unknown etiology CEA behaved as in bacterial pneumonias . Maximal values between 5 and 15 micrograms/l CEA were common in pneumonia, the basal level usually being less than 5 micrograms/l . The severity of pneumonia, as judged by maximal erythrocyte sedimentation rate, correlated weakly with CEA levels in the bacterial group (p less than 0.05) . In pneumonias of unknown etiology white blood cell counts and C-reactive protein levels correlated significantly with maximal CEA (p less than 0.01) . In conclusion we have demonstrated, that in pneumonias of different etiology strongly but transiently increased blood CEA levels are the rule . The severity of pneumonia is not clearly correlated with CEA levels.

Res Exp Med (Berl), 1986, 186(5), 317 - 24
Experimental gram-negative peritonitis: decreased thromboplastin activity in organs with a simultaneous rise of thromboplastin in blood monocytes and peritoneal macrophages; Almdahl SM et al.; Thromboplastin values in blood monocytes, peritoneal macrophages, and in tissue samples from lung, aortic wall, liver, spleen, pancreas, kidney, jejunum, and colon were determined at 4, 10, and 16 h after induction of acute peritonitis (cecal perforation) or sham operation in rats . A maximum 35-fold and 100-fold rise of values was respectively demonstrated in monocytes and peritoneal macrophages in septic animals as compared to controls . This monocyte-macrophage-derived thromboplastin is probably central to the activation of blood coagulation and fibrin depositions/adhesion formation in septic peritonitis . A simultaneous and significant fall in thromboplastin content of standardized specimens from lung, aortic wall, liver, spleen, pancreas, and jejunum was observed in rats with peritonitis . This could reflect mobilization of thromboplastin in favor of the infectious focus . No significant changes were detected in tissue from kidney, whereas samples from the colon of septic animals showed a consistent increase as compared to controls.

Antonie Van Leeuwenhoek, 1986, 52(4), 309 - 18
Degradation of 4-hydroxyphenylacetate by Xanthobacter 124X . Physiological resemblance with other gram-negative bacteria; van den Tweel WJ et al.; Xanthobacter 124X when grom on 4-hydroxyphenylacetate was able to hydroxylate this compound yielding homogenisate . Ring fission of this latter compound gave maleylacetoacetate which was isomerized to fumarylacetoacetate . The isomerase involved resembled maleylacetoacetate isomerases in Gram-negative bacteria in that glutathione was required for activity . Fumarate and acetoacetate were both detected as products of the hydrolysis of fumarylacetoacetate.

Childs Nerv Syst, 1986, 2(1), 26 - 31
Purulent meningitis in the newborn; Karan S; Neonatal meningitis is characterized by unusual clinical manifestations caused by unusual organisms (with a marked predominance of gram-negative organisms), a poor prognosis due to the failure of antibiotics to penetrate the blood-brain barrier, and frequent complications (ventriculitis, hydrocephalus, and brain damage) . The literature is reviewed and our personal experience described . The clinical and bacteriological findings, the complications and results of various therapeutic regimes, and the factors affecting prognosis are discussed.

Scand J Infect Dis, 1986, 18(3), 265 - 7
Fatal septicaemia caused by DF-2 in a previously healthy man; Pers C et al.; A case of fatal septicaemia caused by DF-2, a fastidious gram-negative rod is presented . Attention is drawn to the connection between DF-2 septicaemia and dog bites or contacts, not only in patients with impaired host defence but also in previously healthy individuals . As the organism is difficult to subculture, infections with DF-2 may easily be overlooked.

Oncology, 1986, 43(4), 216 - 8
Failure of allopurinol to provide clinically significant protection against the hematologic toxicity of a bolus 5-FU schedule; Garewal H et al.; Allopurinol has been shown to ameliorate the myelotoxicity of 5-fluorouracil (5-FU) given as an infusion . To study the potential effectiveness of allopurinol in modifying the toxicity of 5-FU given as a bolus, 8 adult patients with metastatic malignancies were given 11 courses of bolus 5-FU with allopurinol . Allopurinol was administered at a dose of 900 mg/day orally beginning a week prior to the 5-FU therapy and continued a week after the last dose of 5-FU was administered . Three patients received a total of 5 courses of 600 mg/m2 of 5-FU via bolus injection for 4 consecutive days every 28 days . Six patients were given 6 courses of 800 mg/m2 of 5-FU via bolus injection in the same schedule . Gastrointestinal toxicity was mild and no significant neurotoxicity was documented . However, severe myelosuppression occurred at the 800 mg/m2 dosage which led to marked leukopenia in 5 of the 6 patient courses and thrombocytopenia in 1 . Gram-negative sepsis developed in 3 of the leukopenic patients with 2 resultant deaths . Allopurinol does not appear to allow clinically significant dose escalation of bolus 5-FU given on this schedule.

Circ Shock, 1986, 19(2), 195 - 201
Endotoxin lethality is intensified by inhibited gluconeogenesis; Kuttner RE et al.; There are two major etiologies regarding the lethal element in the pathophysiology of endotoxemia and severe gram-negative sepsis: 1) metabolic lesions culminating in terminal hypoglycemia and 2) circulatory deficits resulting in early peripheral and late vital organ perfusion failure . Although not mutually exclusive, a direct test of the relative importance of either hypothesis is needed . The impact of inhibited gluconeogenesis on endotoxin lethality in young adult male rats (180-220 g) was investigated . Fasted rats received 20 mg/kg intravenous E . coli endotoxin (LD10) simultaneously with 500 mg/kg intraperitoneal L-tryptophan . This amino acid rapidly forms quinolinic acid, which blocks liver glucose synthesis . Endotoxin together with tryptophan caused hypoglycemic convulsions, killing 22 of 24 rats, 75% within 6 hours . In parallel studies, liver intermediates were assayed in freeze-clamped samples obtained at 5 hours from ether anesthetized rats . The high-energy intermediate phosphoenolpyruvate was 222 +/- 79 nmole/gm +/- 1 S.D . wet liver in the moderately endotoxic rats (N = 8) . In the endotoxin-plus tryptophan group (N = 7), the PEP intermediate had fallen to 58 +/- 24 nmole/gm liver (P = 0.005) . Liver lactate was increased 2.8-fold over the value in the endotoxin-only group, to 4390 nmole/gm wet tissue, showing the failure to utilize gluconeogenic precursors . Tryptophan given alone was not lethal . It is concluded that inhibited gluconeogenesis greatly intensifies the hepatic metabolic derangement of endotoxemia.

J Gen Microbiol, 1986 Jan, 132 ( Pt 1), 103 - 9
Ultrastructure and chemical composition of lipopolysaccharide extracted from Leptospira interrogans serovar copenhageni; Vinh T et al.; Lipopolysaccharide (LPS) from Leptospira interrogans serovar copenhageni was prepared from the aqueous phase of a phenol/water extract . Electron microscopic examination of negatively stained LPS showed a mixture of ribbon-like, round and ring structures . Carbohydrate analysis of the preparations revealed pentoses, hexoses, heptoses, hexosamines, and a 2-keto-3-deoxyonic acid which was chromatographically different from authentic 2-keto-3-deoxyoctonic acid (KDO) . The major fatty acids of the LPS were hydroxylauric, palmitic and oleic acids . Although the leptospiral LPS preparations did not contain KDO or hydroxymyristic acid, they were otherwise morphologically and chemically similar to the LPS of other Gram-negative bacteria.

Folia Parasitol (Praha), 1986, 33(1), 87 - 95
Some diagnostic, biologic and morphologic characteristics of Francisella tularensis strains isolated from the ticks Ixodes ricinus (L.) in the Prague agglomeration; Malkova D et al.; Four infectious agents were isolated from the ticks Ixodes ricinus (L.) collected in the recreational area and park-forest of Prague . On the basis of cultivation, staining, biochemical, serologic properties, pathogenicity for animals and histological tests they were identified as Francisella tularensis with the following features: they are short, gram-negative rods of approximate dimensions of 0.3 X 0.8 micron, growing in enriched media after 3-4 day incubation at 37 degrees C . They form small circular, at first transparent, later greyish turbid colonies with regular rims . They are little active biochemically . They are susceptible to streptomycin and some broad spectrum antibiotics . They react positively with tularemic serum, but in lower titres than those in which this serum reacts with standard antigen . The microbes are highly pathogenic for mice, guinea-pigs, young rats, in which a massive bacteriemia occurs before death, but they do not kill rabbits . They multiply well in chick embryo, but do not grow in cell or tissue cultures . The most important histologic changes were observed in liver and spleen of mice . No pathologic changes were found in brain, lungs, heart, kidneys . Necroses were found in liver and in their marginal zones the microbes were present . Conspicuous were changes in numerous hepatocytes which became enlarged due to microbial multiplication and finally transformed into "sacs" packed with microbes . Histological and electronoptical examination showed that these are intracellular parasites fringed with a light lytic zone . Discussed is the problem to what extent the properties of the isolated strains are typical of F . tularensis as well as the importance of their detection from the aspect of epidemiology and differential diagnostics.

Infect Control, 1986 Jan, 7(1), 23 - 6
Alteration of normal gastric flora in critical care patients receiving antacid and cimetidine therapy; Donowitz LG et al.; One hundred fifty-three critical care patients with documented cimetidine and antacid use were prospectively studied with serial gastric pH determinations and semiquantitative gastric fluid cultures . This study documents the abnormal gastric colonization of patients with therapeutically altered gastric acidity by hospital acquired gram negative rods (GNR) . Three hundred twenty-four gastric fluid cultures from 153 patients revealed 152 (47%) positive cultures for GNR, 78 (24%) sterile specimens, and 94 (29%) positive for mixed oropharyngeal flora . One hundred forty (59%) of the 236 cultures at a pH of 4 or greater were positive for GNR . In contrast, only 12 (14%) of the 88 cultures at a pH of less than 4 were positive for GNR (p less than .001) . Forty-six (52%) of 88 cultures at a pH of less than 4 were sterile as compared to only 32 (14%) of 236 sterile cultures at a pH of 4 or greater (p less than .001) . At low pH, cultures are predominantly sterile and at a pH of 4 or greater the flora dramatically changes to hospital acquired GNR . This artificially maintained reservoir of gram negative rods in the critically ill patient is a potential reservoir of organisms causing nosocomial bacteremia or pneumonia in this high risk population.

Gene, 1986, 48(1), 119 - 31
Molecular cloning of the plasmid RP4 primase region in a multi-host-range tacP expression vector; Furste JP et al.; Plasmid RP4 primase was overproduced by utilizing autoregulated high-level expression vector systems in Escherichia coli and in four other Gram-negative bacterial species . Analysis of the products in E . coli revealed that in addition to the two primase polypeptides of 118 and 80 kDa the pri region of RP4 encodes two smaller proteins of 16.5 and 8.6 kDa . The transcript for the four RP4-specified products is polycistronic . The vector system used in E . coli is based on the plasmid pKK223-3 (Brosius and Holy, 1984), a ColE1-type replicon which contains a polylinker sequence flanked on one side by the controllable tac promoter and on the other side by two strong transcriptional terminators . The gene for the lac repressor (lacIQ) was inserted to render the use of the plasmid independent from repressor-overproducing strains . The gene cartridge essential for high-level expression and selection was combined with the RSF1010 replicon to generate a vector plasmid functioning in a wide variety of Gram-negative hosts . The versatility of the vector family was extended by constructing derivatives that contain the polylinker in inverted orientation relative to the tac promoter . Therefore, the orientation of the cloned fragment can be chosen by 'forced cloning' into the appropriately selected vector.

Antonie Van Leeuwenhoek, 1986, 52(6), 537 - 42
Use of mucin and hemoglobin in experimental murine gram-negative bacteremia enhances the immunoprotective action of antibodies reactive with the lipopolysaccharide core region; Appelmelk BJ et al.; An antiserum with a high content of antibodies, binding to the Gram-negative lipopolysaccharide core region, was prepared by immunizing rabbits with the rough Escherichia coli mutant J5 . This antiserum was capable of protecting mice against lethal challenge doses of E . coli 0 111:B4 in a mouse model where the animals were compromised by means of mucin plus hemoglobin (LD 50 = 10(3) bacteria) . However, no protection was observed in a non-compromised mouse model (LD 50 = 10(7) bacteria) . This observation might explain why in the past so many discrepant results have been obtained in mouse protection studies with cross-reactive antisera.

J Hyg Epidemiol Microbiol Immunol, 1986, 30(3), 287 - 93
Fatty acid composition of bacteria as a chemotaxonomic criterion; Vasyurenko ZP et al.; The paper reviews data on the fatty acid composition of bacteria as a taxonomic criterion useful for the identification of bacteria and specifying their classification . Variations in the fatty acid composition of bacteria associated with culturing conditions and due largely to the adaptive role of fatty acids in the bacterial cell require that standard conditions be maintained while examining that character . In some cases, adjustment of culturing conditions may be a factor providing for the identification of specificities in the fatty acid profile of bacteria of related species . The use of data on the fatty acid composition of bacteria has promising applications in confirming and establishing their phylogenetic relationship, that being accomplished not only on the basis of similarity in the character under consideration which correlates with similarity in genotypic and other phenotypic characters, but by analyzing its adaptive variability as well . The latter approach is especially promising for creating a natural classification . It is pointed out that the determination of the fatty acid composition of the lipid component of lipopolysaccharides from Gram-negative bacteria is useful as it supplies additional taxonomic information.

Res Exp Med (Berl), 1986, 186(3), 229 - 38
The role of the spleen and splenic autotransplants in clearing experimental bacteremia caused by the gram-negative bacterium Escherichia coli; Thalhamer J et al.; Several clinical and laboratory studies have demonstrated the risk of sepsis in connection with encapsulated bacteria . The importance of clearing these organisms by the spleen is now well accepted . In contrast, the present work deals with the clearance of non-encapsulated gram-negative bacteria (Escherichia coli) . The animals used for the experiments (a heterogeneous population of rabbits) were divided into a control group, a splenectomized group, and an autotransplanted group . The histological examination of the splenic transplants revealed typical splenic tissue including lymphatic follicles with germinal activity 42 days after transplantation . For estimation of the clearance capacity different amounts of bacteria were injected i.v . into the rabbits, and colony-forming bacterial cells in the blood were counted at certain intervals . In the control group no bacteria could be detected in the blood after 7 min . All animals of the splenectomized and autotransplanted groups showed a remarkable decrease in clearance efficiency (no bacteria in the blood after 19 min) . No difference in the clearance kinetics could be shown between splenectomized and autotransplanted animals . Measuring the uptake of bacterial cells into different organs elicited low incorporation in the spleen as compared to non-immunocompetent organs, but no difference between normal spleen and splenic replants . However, saturation with E . coli cells reached higher limits in the normal spleen than in autotransplants . The immunologic capacity with respect to IgM-producing lymphocytes was measured by the hemolytic plaque assay . The results showed a severe malfunction of the autotransplants as compared to the normal spleen (only 2% of the activity of the control group) . Vaccination against E . coli increased the clearance efficiency in all three groups . The data presented in this paper point out that several functions of the spleen cannot be carried out by autotransplants . The reasons, therefore, may be limited transplant mass and/or decreased specific functions.

Toxicol Pathol, 1986, 14(1), 66 - 72
Aminoglycoside nephrotoxicity; Hottendorf GH et al.; Aminoglycosides are life-saving antibiotics in patients with gram negative sepsis . Renal dysfunction occurs in approximately 10% of all clinical courses of aminoglycosides . Because of close pharmacokinetic and toxicologic similarities, rats are excellent human surrogates for comparing the nephrotoxic potentials of these antibiotics . Comparisons in rats are also more sensitive than clinical comparisons due to the insensitivities of clinical renal function tests, the confounding influences present in seriously-ill patients and the inability to make morphologic comparisons in the clinic . The pathogenesis of aminoglycoside nephrotoxicity is still evolving despite extensive world-wide investigations . However, these investigations have facilitated the identification of several inhibitors of aminoglycoside nephrotoxicity . The clinical usefulness of these inhibitors must still be established.

Jpn J Antibiot, 1986 Jan, 39(1), 159 - 76
{Efficacy evaluation of aztreonam for suppurative otitis media}; Baba S et al.; Preclinical and clinical studies were performed to evaluate usefulness and safety of aztreonam (AZT) in the treatment of acute otitis media, acute exacerbation of chronic otitis media and chronic otitis media and the following results were obtained . MICs for P . aeruginosa, P . mirabilis and P . inconstans isolated from the patients with suppurative otitis media were 1.56 micrograms/ml, less than or equal to 0.025 micrograms/ml and less than or equal to 0.025 micrograms/ml respectively in their peaks . In the intravenous injection of 1 g, AZT concentration in the mastoid cell mucosa was 7.52 micrograms/g on average and serum concentration 51.6 micrograms/ml sufficiently suggesting clinical efficacy of AZT . In the clinical trial by administering AZT 1-2 g/day for the patients with suppurative otitis media, effective rates were 2/3 (66.7%) for acute otitis media, 16/22 (72.7%) for acute exacerbation of chronic otitis media, 21/34 (61.8%) for chronic otitis media and 6/7 (85.7%) for cholesteatoma of the middle ear . Elimination rate of single Gram-negative pathogens was 82.1% in the bacteriological studies of AZT . As for abnormal laboratory findings, 7 cases showed GOT, GPT elevations . However, they were in minor degree and transient . Side effect was not noted except 1 case of flushing with itching . It was considered from the above results that AZT is a highly useful antibiotic for suppurative otitis media.

J Ocul Pharmacol, 1986 Spring, 2(2), 177 - 84
Retinal toxicity of intravitreal cefoperazone; O'Hara MA et al.; Cefoperazone is a broad spectrum, third-generation cephalosporin with potential usefulness in treating endophthalmitis because of its in vitro activity against Gram-negative organisms . Retinal toxicity was evaluated via serial indirect ophthalmoscopy, electrophysiologic testing and histopathologic examination of 43 Dutch-belted rabbit eyes injected intravitreally with 2, 4, 8, 16 or 32 mg of cefoperazone in a volume of 0.1 cc each . They were compared with seven eyes injected with sterile saline . Results show electroretinographic and histological evidence of retinal toxicity at concentrations of 16 mg or greater, while a single intravitreal dose of 8 mg or less of cefoperazone produced no evidence of retinal toxicity.

Drugs, 1986, 31 Suppl 3, 55 - 63
Plasmid-mediated beta-lactamase in Branhamella catarrhalis; Kamme C et al.; The plasmid-mediated beta-lactamase in Branhamella catarrhalis (BRO-1), also occurring in Moraxella nonliquefaciens, differs from other known plasmid-mediated beta-lactamases in Gram-negative bacteria regarding substrate profile and isoelectric point . B . catarrhalis strains previously reported to produce beta-lactamases deviating from BRO-1 were tested, and the beta-lactamases did not differ significantly from BRO-1 in substrate profile, isoelectric point or relative substrate affinity index (RSAI) . Further investigations of strains of various geographic origin should be undertaken . RSAI seems to be a useful tool for screening of beta-lactamases in B . catarrhalis since values for a large number of strains can easily be determined . The previously reported conjugational transfer of BRO-1 production within species B . catarrhalis and from M . nonliquefaciens to B . catarrhalis was confirmed . Four bands of extrachromosomal DNA were regularly detected by agarose gel electrophoresis in beta-lactamase-producing as well as in beta-lactamase-negative strains of B . catarrhalis and M . non-liquefaciens, provided that the excessive nuclease activity in the preparations was inhibited.

J Child Neurol, 1986 Jan, 1(1), 34 - 7
Suppressed pituitary ACTH response after ACTH treatment of infantile spasms; Ross DL; Suppression of an adrenocorticotropic hormone (ACTH) response to insulin hypoglycemia has been reported in ACTH-treated adults . There are no guidelines for withdrawal of ACTH treatment in children . After observing suppressed morning cortisol in several children, insulin tolerance tests were performed in five children within 48 hours after tapered withdrawal of ACTH treatment for myoclonic seizures . ACTH response, as determined by cortisol and beta-endorphin radioimmunoassay, was adequate in four of the children . One child showed low basal levels and minimal elevation during hypoglycemia for both beta-endorphin (0 to 3 pg/ml) and cortisol (3.6 to 4.4 micrograms/dL) on initial testing, but normal responses six weeks later . Measurement of beta-endorphin response supported a central basis for suppression in the child, who had had an adrenal hemorrhage during gram-negative sepsis while on ACTH . ACTH release is transiently suppressed in some children after exogenous ACTH treatment . Tapered withdrawal and stress coverage is recommended.

Crit Rev Microbiol, 1986, 13(1), 1 - 62
Outer-membrane permeability of bacteria; Nakae T; Gram-negative bacteria evolved to survive under the conditions in which a number of hazardous compounds are abundant . The outer membrane which protects the cell interior acts as a barrier against such hazardous agents, yet the cells must incorporate the chemicals that are essential for the cellular activity . The devices that Gram-negative bacteria developed to incorporate such essence are the transmembrane pores . These pores could be subdivided into three categories: (1) pore made of porins has a weak solute selectivity; (2) pore made of lamB protein and tsx proteins hold intermediate solute specificity . and (3) pores for the diffusion of vitamin B12 and ferric ion-chelator complexes have a tight solute specificity . Porins are identified from a number of Gram-negatives and from the outer membrane of mitochondria of various sources . Studies on the diffusion properties of these outer-membrane proteins provided essential information to understand membrane transports.

J Appl Bacteriol, 1986 Jan, 60(1), 21 - 7
Prediction of the keeping quality of pasteurized milk by the detection of cytochrome c oxidase; Kroll RG et al.; The keeping quality (KQ) of pasteurized milk samples stored at 5 degrees C and 10 degrees C was satisfactorily predicted after 18 h pre-incubation with 0.05% benzalkonium chloride at 20 degrees C, by estimating the numbers of Gram-negative psychrotrophic bacteria using the simple, cheap and rapid (5 min) assay of cytochrome c oxidase . Correlation coefficients for the relationship between cytochrome c oxidase activity at 20 degrees C and KQ at 5 degrees C or 10 degrees C of -0.89 and -0.84 respectively were obtained . The method correctly predicted the KQ of more than 89% of the samples of pasteurized milk . The assay was not satisfactory for use on samples after pre-incubation at 30 degrees C.

Arch Dermatol Res, 1986, 278(4), 307 - 13
Treatment of gram-negative folliculitis with isotretinoin; Neubert U et al.; The clinical and bacteriological findings are reported in 13 patients with gram-negative folliculitis before, during, and after treatment with isotretinoin (13-cis-retinoic acid) . Patients were treated for 14-36 weeks with a daily dose of 0.5-1.5 mg isotretinoin/kg body weight . Inflammatory lesions were counted before and during weeks 2, 4, 8, 12, 16, 20, 24, 28, and 30 of therapy and again up to 172 weeks after cessation of treatment . In all patients there was an impressive improvement in clinical symptoms, especially a decrease in seborrhea and inflammatory lesions . Simultaneously, the gram-negative bacteria disappeared from the facial skin . Full clinical bacteriological remission was achieved in 9 patients within a period of up to 43 months, with minor recurrences of the disease in the remaining 4 patients.

Am J Med Sci, 1986 Jan, 291(1), 29 - 38
Effects of ibuprofen on endotoxin-induced alveolitis: biphasic dose response and dissociation between inflammation and hypoxemia; Rinaldo JE et al.; Ibuprofen is a cyclo-oxygenase inhibitor that is alleged to have additional direct effects on leukocyte function . These properties suggest that Ibuprofen may be of potential therapeutic value for neutrophil (PMN)-mediated acute lung injury in humans such as that resulting from septicemia by gram-negative organisms . This study quantitated the effect of pretreatment with Ibuprofen on the intensity of acute neutrophilic alveolitis following endotoxemia . The effect of Ibuprofen on neutrophilic alveolitis was biphasic: There was suppression of inflammation at a high dose (30 mg/kg), enhancement at a low dose (3 mg/kg), and intermediate doses (10-20 mg/kg) had no effect . In contrast, both 10 and 30 mg/kg of Ibuprofen prevented early hypoxemia following endotoxemia, suggesting that early hypoxemia and inflammation by neutrophils were not causally related . The dose of Ibuprofen required to suppress neutrophil alveolitis exceeds that required to inhibit cyclooxygenase in the model . Therefore, suppression of alveolitis by 30 mg/kg of Ibuprofen may depend on other pharmacologic properties of Ibuprofen such as its direct effect on neutrophil migration.

Am J Otolaryngol, 1986 Jan-Feb, 7(1), 42 - 6
Effect of endotoxin on keratin production of keratinocytes in vitro; Sugita T et al.; The rate of keratin protein accumulation appears to be a crucial factor in the pathogenesis of middle ear cholesteatoma . The effect of endotoxin on keratin production of keratinocytes was studied . Endotoxins are lipopolysaccharides contained within the cell wall of gram-negative bacteria . Various concentrations of endotoxin were added to keratinocytes derived from newborn rats . Syntheses of keratin proteins were studied by incorporation of 3H-leucine into each protein fraction . Extraction of keratin proteins with various salt solutions showed that endotoxin stimulated keratinocytes to produce keratohyalin granules and its related proteins as well as proteins in the stratum corneum (keratin proteins) . These findings suggest that accumulation of keratin debris in cholesteatoma may result from the effect of infection in the epithelial cells.

J Biol Chem, 1985 Dec 15, 260(29), 15536 - 41
The biosynthesis of gram-negative endotoxin . Formation of lipid A precursors from UDP-GlcNAc in extracts of Escherichia coli; Anderson MS et al.; The Gram-negative bacterium Escherichia coli has previously been shown to utilize two unique glucosamine (GlcN)-derived phospholipids in the biosynthesis of lipid A disaccharides (Bulawa, C.E., and Raetz, C . R.H . (1984) J . Biol . Chem . 259, 4846-4851; Ray, B . L., Painter, G.L., and Raetz, C.R.H . (1984) J . Biol . Chem . 259, 4852-4859 . We now present evidence that these compounds, UDP-2,3-diacyl-GlcN and 2,3-diacyl-GlcN-1-phosphate (2,3-diacyl-GlcN-1-P), are generated in extracts of E . coli by fatty acylation of UDP-GlcNAc . The initial reaction is an O-acylation of the glucosamine ring, presumably of the 3-OH group, with (R)-beta-hydroxymyristate, followed by removal of the acetyl moiety, and further fatty acylation of the N atom with (R)-beta-hydroxymyristate to yield UDP-2,3-diacyl-GlcN . Hydrolysis of the pyrophosphate bridge in this molecule gives 2,3-diacyl-GlcN-1-P + UMP . In vivo pulse labeling with 32Pi supports this postulated pathway, since UDP-2,3-diacyl-GlcN is labeled prior to 2,3-diacyl-GlcN-1-P . UDP-glucosamine is inactive as a substrate in the initial acylation reaction . These acylations show an absolute specificity for fatty acyl moieties activated with acyl carrier protein . No reaction is detected with fatty acyl-CoA or free fatty acid . The fatty acylation of sugar nucleotides has not been reported previously in E . coli or any other organism.

J Appl Physiol, 1985 Dec, 59(6), 1726 - 32
Pulmonary pathophysiological changes in sheep caused by endotoxin precursor, lipid X; Burhop KE et al.; The chemical structure of the biologically active lipid A portion of Gram-negative endotoxin {lipopolysaccharide (LPS)} has recently been elucidated . This was greatly facilitated by the isolation of an Escherichia coli mutant that accumulates large quantities of lipid X, a novel monosaccharide precursor of lipid A (C . R . H . Raetz, Rev . Infect . Dis . 6: 463-471, 1984) . We now report on the activity of lipid X in the lung-lymph model in sheep . We have measured the response to cumulative bolus injections of lipid X (2,3-diacylglucosamine 1-phosphate) in six chronically instrumented unanesthetized sheep . Lipid X at a total dose of 40 micrograms/kg produced a biphasic pattern of changes . The early phase was characterized by a rapid transient pulmonary arterial constrictive response that was dose dependent, accompanied by a delayed transient increase in lung-lymph flow (P less than 0.05), a significant (P less than 0.01) decrease in arterial blood O2 tension and an increase (P less than 0.05) in lung-lymph protein clearance . Protein permeability changes in the first phase are not usually seen following endotoxin injection . However, like endotoxin, lipid X also produced a late phase (3-6 h later) of increased lung vascular permeability to fluid and protein as reflected by significant (P less than 0.05) increases in both lung-lymph flow and lung-lymph protein clearance in the presence of stable pulmonary vascular pressures at or below base-line levels . We conclude that some of the pulmonary pressor activity of the endotoxin molecule can be attributed to the lipid X substructure . Furthermore, changes in vascular permeability may also be initiated by this substance.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1985 Dec, 182(1), 33 - 8
{Differentiation of nonfermenting gram-negative human-pathogenic rod bacteria from sewage water}; Geiss HK et al.; In the present paper the examination of the new microidentification-system API 20 NE for clinically important nonfermenters is reported . The origin of all strains tested was non-clinical (sewage, tap-water, food-stuff and other environmental sources) . One hundred thirty four strains were examined simultaneously in the API 20 NE and by standard tests . One hundred twenty three strains, which included 23 species could be identified conformably . Out of 11 strains, not or misidentified in the API-system only 2 could be classified to species level by conventional means, the remainder were diagnosed to genus level only . Causes are discussed . Our data suggest that the API 20 NE is also a useful aid in routine diagnosis in environmental hygiene for clinically important nonfermenters . It allows a short-time-diagnosis with a high degree of specificity and reliability.

Proc Natl Acad Sci U S A, 1985 Dec, 82(24), 8767 - 70
"Frizzy" genes of Myxococcus xanthus are involved in control of frequency of reversal of gliding motility; Blackhart BD et al.; Myxococcus xanthus, a Gram-negative bacterium, has a complex life cycle that includes fruiting body formation . Frizzy (frz) mutants are unable to aggregate normally, instead forming frizzy filamentous aggregates . We have found that these mutants are defective in the control of cell reversal during gliding motility . Wild-type cells reverse their direction of gliding about every 6.8 min; net movement occurs since the interval between reversals can vary widely . The frzA-C, -E and -F mutants reverse their direction of movement very rarely, about once every 2 hr . These mutants cannot aggregate normally and give rise to frizzy filamentous colonies on fruiting agar or motility agar . In contrast, frzD mutants reverse their direction of movement very frequently, about once every 2.2 min; individual cells show little net movement and form smooth-edged "nonmotile" type colonies . Genetic analysis of the frzD locus shows that mutations in this locus can be dominant to the wild-type allele and that its gene product(s) must interact with the other frz gene products . Our results suggest that the frz genes are part of a system responsible for directed movement of this organism.

Diabetes, 1985 Dec, 34(12), 1253 - 9
Endogenous gut-derived bacterial endotoxin tonically primes pancreatic secretion of insulin in normal rats; Cornell RP; This laboratory has proposed that endogenous gut-derived bacterial endotoxin primes the pancreatic secretion of insulin in normal rats . Endogenous lipopolysaccharide (LPS) is continually absorbed from the gut into intestinal capillaries, and low-grade portal venous endotoxemia is the status quo . Under physiologic conditions, Kupffer cells of the liver totally phagocytize and degrade endotoxin from the portal circulation . Evidence from this and other laboratories indicates that administration of exogenous LPS to humans and rats enhances pancreatic secretion of both insulin and glucagon . Conversely, findings of the present study demonstrate that restriction of endogenous LPS in fasted rats depresses the basal and arginine-stimulated concentrations of plasma insulin . Techniques used to restrict gut-derived LPS availability included chronic daily gavage with neomycin and cefazolin for gut sterilization and with cholestyramine or lactulose to reduce endotoxin within the gut . In addition, induction of endotoxin tolerance was produced by progressively higher doses of LPS intraperitoneally (i.p.), and polymyxin B was administered subcutaneously (s.c.) daily to neutralize the lipid A portion of circulating LPS . Finally, isolator-reared, defined flora rats, which were gram-negative-bacteria-deficient, and, therefore, LPS-deficient, were compared with conventional counterparts . Basal plasma insulin but not glucagon levels were consistently and significantly reduced in endogenous LPS-restricted animals . Glucose-stimulated plasma insulin was decreased only after parenteral treatment by tolerance induction and polymyxin B administration . Both plasma insulin and glucagon were depressed in response to arginine challenge in most LPS-restricted rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Jpn J Antibiot, 1985 Dec, 38(12), 3561 - 72
{Clinical evaluation of aztreonam in the field of obstetrics and gynecology}; Cho N et al.; Aztreonam (AZT), a new monobactam antibiotic was evaluated on clinical efficacy and bacteriological response in gynecological and obstetrical infections, and the following results were obtained . AZT was given to 22 cases with obstetrical and gynecological infections at a dose of 1 g X 2 times daily and 86.4% of clinical efficacy, 45.5% of eradicated rate on diagnosis, 52.5% of bacteriological response on isolated organisms and 83.3% of bacteriological effect on cases isolated Gram-negative bacteria were assessed . Side effect incidence was very low.

Jpn J Antibiot, 1985 Dec, 38(12), 3542 - 60
{Preclinical and clinical studies on aztreonam in the field of obstetrics and gynecology}; Obata I et al.; Penetration of aztreonam (AZT) into the uterus and the adnexal tissues and usefulness and safety of AZT for obstetric and gynecologic infections were studied with the following results . By one shot intravenous injection of AZT 1 g, the uterus and the adnexal tissues showed favorable penetration with Cmax 27.0-48.5 micrograms/g, AUC 29.4-84.9 micrograms X hr/g and Tmax 0.10-0.44 hours . MIC50, MIC80 and MIC90 of AZT for Gram-negative bacteria measured prior to administration were very low being 0.10 micrograms/ml, 0.20 micrograms/ml and 1.56 micrograms/ml, respectively . Clinical effect of AZT for 30 infection cases in obstetrics and gynecology was evaluated according to an overall efficacy criteria resulting in "good" for all the cases . With regard to microbiological effect, 90.9% of the pathogens isolated prior to the administration were eliminated by AZT . During and after the administration of AZT, side effect due seemingly to AZT was not observed in subjective and objective symptoms and laboratory values.

Jpn J Antibiot, 1985 Dec, 38(12), 3505 - 12
{Fundamental and clinical studies on aztreonam in obstetrics and gynecology}; Shimizu T et al.; Aztreonam (AZT), a monobactam antibiotic, is known to have a high activity against Gram-negative bacteria . Fundamental and clinical studies were carried out on AZT with the following results . Following 1 g of bolus intravenous injection, the transfer of AZT to uterine artery and internal genital organs was found to be satisfactory . The levels of the drug in uterine artery showed 34.28, 4.50 micrograms/ml at approximately 2, 6 hours, and those in internal genital organs showed 3-34 micrograms/g at 2 hours . Clinical efficacy was; excellent in 4 cases, good in 13 cases and poor in 1 case, with the very high overall efficacy rate of 94.4% . Abnormal laboratory findings and side effects due to the drug were not noted.

Vestn Khir Im I I Grek, 1985 Dec, 135(12), 66 - 9
{Characteristics of sepsis in burn patients today}; Vazina IR et al.; An analysis of lethal outcomes following thermal traumas during the recent 8 years has shown sepsis to occupy one of the leading places as a cause of death of burned people . During the recent years the incidence of early sepsis has been increased . This kind of sepsis develops in the period of shock and acute toxemia, is often of lightening character, possesses certain specific morphological features and is caused predominantly by gram-negative flora threatening to patients with critical burns of more than 40% of the body surface.

Cutis, 1985 Nov 15, 36(5A), 13 - 4
Diagnosis and treatment of osteomyelitis; Norden CW; The diagnosis and management of osteomyelitis continues to present problems . Technetium bone scans may identify acute osteomyelitis before the characteristic disease changes are visible on x-ray studies, but they have a number of drawbacks . Microbiological studies are critical in making precise diagnoses of the cause so that proper therapy will be given . In treatment of acute osteomyelitis, several investigators report good results from four-week administration of parenteral antibiotic, or one week of parenteral treatment followed by three weeks of oral therapy . Chronic osteomyelitis requires surgical removal of dead tissue followed by lengthy parenteral and oral antibiotic therapy . Chronic forms of the disease caused by resistant gram-negative organisms may prove responsive to quinoline therapy . These agents may attain inhibitory levels on oral administration, and have proved to be effective in animal models . Clinical trials, however, are required to determine their usefulness in the treatment of clinical disease.

Biochem Pharmacol, 1985 Nov 15, 34(22), 3995 - 8
Dose-dependent reduction of lipopolysaccharide pyrogenicity by polymyxin B; Warner SJ et al.; Lipopolysaccharides (LPS) from Gram-negative bacteria are potent pyrogens in mammals . Polymyxin B (PB), a cationic polypeptide antibiotic, binds lipid A, the active moiety of LPS, with high affinity and abrogates several biological responses to LPS . We studied the effect of PB on pyrogenicity of purified LPS from E . coli 0111:B4 in rabbits . PB reduced the pyrogenic response to LPS in a dose-dependent manner at mass ratios (PB:LPS) from 5:1 to 100:1 . Previous reports have suggested that PB is effective only at much higher doses . In our hands, PB itself is pyrogenic, unless previously gamma-irradiated . Our results confirm in vivo the anti-endotoxic action of PB.

Jpn J Antibiot, 1985 Nov, 38(11), 3230 - 8
{Fundamental and clinical studies on aztreonam in pediatrics}; Sunakawa K et al.; Fundamental and clinical results of AZT in pediatrics were as follows . Pharmacokinetics of AZT was studied for 1 case with resulting high serum concentration and a half-life of approximate 1 hour . AZT was administered to 10 patients with bacterial infections with 100% clinical efficacy and 62.5% bacterial elimination . Side effect was 1 case of diarrhea . There were no abnormal laboratory or coagulation test findings nor vitamin K deficiency, platelet hypofunction or effects on intestinal bacterial flora . AZT was considered to be high in safety . The administration of 20 mg/kg AZT 3 times a day was considered to be an effective treatment for pediatric Gram-negative infections.

Jpn J Antibiot, 1985 Nov, 38(11), 3217 - 29
{Clinical and pharmacokinetic evaluations of aztreonam in children}; Meguro H et al.; Aztreonam (AZT) was evaluated for its safety, clinical efficacy and pharmacokinetics in children . AZT was effective in all the 16 children with Gram-negative bacterial infections . The diagnoses included acute bronchitis and pneumonia (11), UTI (2), UTI with bacteremia (1), purulent meningitis (1) and acute mucositis (1) . The etiologic agents were H . influenzae (10), B . catarrhalis (1), N . meningitidis group C (1), E . coli (3) and P . aeruginosa (2) . The serum half-life was approximately 1.2 hours after intravenous bolus injection . Penetration into the inflamed cerebrospinal fluid was good not only in acute purulent meningitis but also in viral meningitis . From the present study, AZT is a safe and effective antibiotic when used in children with Gram-negative bacterial infections.

Jpn J Antibiot, 1985 Nov, 38(11), 3145 - 55
{A clinical study of cefotaxime in patients with infections complicating a disorder of the hemopoietic tissue . Its therapeutic effect and influence on the coagulation system}; Kaneko H et al.; Twenty infectious episodes were caused mainly by Gram-negative rods in 16 patients with a disorder of the hemopoietic tissue . The ages of the patients ranged between 20 and 76 years . Cefotaxime (CTX) was used alone in 9 infectious episodes (group I) and in combination with other antibiotics in the remaining 11 infectious episodes (group II) . The following results were obtained . A good response to CTX was noted . The clinical and bacteriological success rates were 100% and 83% in group I, and 82% and 100% in group II, respectively . Bleeding was not clinically found during and after treatment of any infectious episodes with CTX . No change in PT and aPTT was noted during CTX treatment, either . CTX was thus evaluated to be an effective and safe cephem antibiotic in the treatment of infectious episodes secondary to a disorder of the hemopoietic tissue, which is usually accompanied by a marked hemorrhagic tendency.

Am J Hosp Pharm, 1985 Nov, 42(11), 2472 - 8
Outcome of patients treated by an aminoglycoside pharmacokinetic dosing service; Sveska KJ et al.; Differences in outcome between patients whose aminoglycoside dosing regimens were individualized by a clinical pharmacokinetic dosing service (CPDS) and patients who did not receive CPDS consultation were evaluated by retrospective chart review . Data for a number of dependent variables that might affect patient outcome were collected from the medical records of 42 patients with culture-proven gram-negative pneumonia or sepsis who had received CPDS dosing consultations and 60 similar patients who had not received CPDS consultations . Data were also collected for a number of analytical and categorical independent variables to evaluate sources of variation between the groups . Variables were compared using both parametric and nonparametric statistical tests . For patients whose dosing regimens had been individualized by the CPDS, length of aminoglycoside therapy and length of stay were significantly shorter, changes in serum creatinine concentration from baseline were significantly smaller, and mortality was significantly lower; morbidity was reduced by significantly fewer incidences of aminoglycoside nephrotoxicity . Significant differences existed between the mean dosing intervals, mean numbers of serum aminoglycoside concentration determinations, and mean baseline serum creatinine concentrations for the two groups . Although a favorable difference in patient outcome was demonstrated for patients whose dosing regimens were individualized by the CPDS, unmeasurable differences between the two groups of patients make it difficult to attribute the difference solely to the effect of the dosing service.

J Oral Pathol, 1985 Nov, 14(10), 793 - 9
In vitro attachment of bacteria to extracts of cementum; Somerman MJ et al.; Cementum is a specialized mineralized tissue providing for the attachment of periodontal fibers to the root surface of a tooth . In periodontal disease this connective tissue attachment to the cemental surface is lost . The ability of bacteria to adhere to the root surface, an initial event in the disease process, may be influenced by the organic matrix of cementum . Therefore, an in vitro assay of cell attachment was modified to study bacterial adherence to protein extracts of cementum . Petri dishes coated with the extracts were pre-incubated in culture media and then bacteria were added . Using this assay, Capnocytophaga-like species, a gram negative bacterium implicated in periodontal disease, attached preferentially to dishes coated with cemental extracts when compared with Type I collagen or uncoated dishes . This assay system should prove beneficial for studying the attachment of various microorganisms to protein extracts of both normal and diseased cementum, as well as providing insight into the unique attachment properties of cementum.

Rev Infect Dis, 1985 Nov-Dec, 7 Suppl 4, S803 - 9
Clinical evaluation of aztreonam therapy for serious infections due to gram-negative bacteria; McKellar PP; Aztreonam--a new, synthetic, monocyclic beta-lactam antibiotic with excellent in vitro activity and beta-lactamase stability--was used for the treatment of 26 serious infections due to gram-negative bacteria in 23 patients: nine cases of bacteremia, one of endocarditis, one of pneumonia, one of septic arthritis, six of osteomyelitis, five of abscess or soft tissue infection, and three of meningitis . The majority of patients had serious underlying disease, and 18 were in critical or poor condition . The mean age of the patients was 62 years, and the mean duration of therapy was 19 days . The clinical condition of all 23 patients improved during therapy; 20 infections were cured according to clinical criteria . Three of the six instances of therapy failure were due to inadequate debridement . No superinfections, resistant pathogens, or significant adverse reactions were seen . Aztreonam was effective and safe for the treatment of serious gram-negative infections.

Am J Physiol, 1985 Nov, 249(5 Pt 2), R563 - 9
Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration; Cornell RP; The influence of restricting gut-derived endotoxin availability on liver regeneration after partial hepatectomy was evaluated . Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats . Liver regeneration was quantified after partial hepatectomy by {3H}thymidine incorporation into hepatic DNA; endotoxemia due to absorption of endogenous endotoxin from the gut into the portal circulation was determined by qualitative lysate assay of perchloric acid-extracted plasma samples, and plasma levels of the hepatotrophic factors insulin and glucagon were measured by radioimmunoassay . Treatments to restrict gut-derived endotoxin included chronic gavage with neomycin and cefazolin for gut sterilization, chronic gavage with cholestyramine to bind endotoxin within the gut, subcutaneous administration of polymyxin B to neutralize the lipid A portion of circulating endotoxin, intraperitoneal induction of endotoxin tolerance by progressively higher doses of endotoxin, and experimentation with isolator-reared defined flora Fisher rats that were Gram-negative bacteria deficient and therefore endotoxin deficient . All treatments to restrict endogenous endotoxin impaired DNA synthesis in regenerating livers particularly 21 h posthepatectomy when replication was increasing most rapidly in normal rats . We hypothesize that impairment of DNA synthesis after partial hepatectomy in endotoxin-restricted animals was due to the observed lack of normal systemic endotoxemic as well as hyperinsulinemic and hyperglucagonemic responses to 67% liver resection.

Infect Immun, 1985 Nov, 50(2), 527 - 33
Endotoxin-induced selective dysfunction of rabbit polymorphonuclear leukocytes in response to endogenous chemotactic factors; Hartiala KT et al.; To assess the mechanism and specificity of polymorphonuclear leukocyte (PMN) dysfunction induced by endotoxin, rabbits were injected intravenously with 100 micrograms of Escherichia coli endotoxin, and PMN function was studied 18 to 24 h later . Compared to PMN from normal rabbits, peripheral blood PMN from rabbits injected with endotoxin showed diminished chemotactic responsiveness to two endogenous peptides, C5a (complement) and platelet-derived growth factor, and to two endogenous lipids, leukotriene B4 and platelet-activating factor . The chemotactic response to the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), was unimpaired . In contrast to migration, endotoxin injection resulted in inhibition of the secretory response to the two endogenous peptides but not to the lipids or to FMLP . At a 1:4 (vol/vol) dilution, the plasma either 1 or 24 h after the endotoxin injection inhibited normal PMN chemotactic responses to C5a but not to FMLP . Similarly, at a 1:10 dilution, this plasma inhibited normal PMN chemotactic responses to leukotriene B4 . The factor responsible for inhibiting responses to leukotriene B4 was anionic, specific for leukotriene B4 responses, and greater than 12,000 daltons . These data may be relevant to understanding PMN dysfunction during gram-negative sepsis.

J Dent Res, 1985 Nov, 64(11), 1306 - 10
The relationship between serum IgG levels to subgingival gram-negative bacteria and degree of periodontal destruction; Naito Y et al.; The relationship between the serum IgG antibody titer against seven species of Gram-negative periodontopathic bacteria and clinical parameters (including plaque index, gingival index, periodontal pocket depth, and alveolar bone loss) was studied in 38 subjects . IgG antibody titer against the sonicated antigens was determined by micro-ELISA . A statistically significant correlation was found between the serum antibody titer against B . gingivalis and the degree of clinical parameters, especially pocket depth . The serum IgG levels against the seven micro-organisms in 16 periodontal patients before and after clinical treatment were also determined . Responses to B . gingivalis decreased (p less than 0.001), whereas responses to E . corrodens (p less than 0.01) increased slightly . No marked differences were noted between pre- and post-treatment sera in titers against B . intermedius, B . loescheii, F . nucleatum, A . actinomycetemcomitans, and C . ochracea.

J Gen Microbiol, 1985 Nov, 131 ( Pt 11), 2953 - 60
Evidence for the presence of cAMP, cAMP receptor and transcription termination factor rho in different gram-negative bacteria; Biville F et al.; Cyclic AMP has been shown to be present in 12 different Gram-negative bacteria and the regulation of its concentration, as a function of growth conditions, is similar to that described for Escherichia coli K12 . Antibodies raised against catabolite activator protein (CAP) and Rho protein of E . coli K12 were used to check for the occurrence of cross-reactive antigens . Using radioimmunological assays, immunoblotting techniques and biochemical criteria we showed a wide distribution of CAP and Rho, structurally and functionally closely related to the corresponding E . coli K12 proteins . These results suggest that transcription is similarly regulated by these factors in Gram-negative bacteria.

Rev Infect Dis, 1985 Nov-Dec, 7(6), 731 - 6
Antigens of Chlamydia trachomatis; MacDonald AB; Chlamydia trachomatis is an obligate intracellular parasite that elaborates antigens on its surface . These antigens are divided into genus-, species-, subspecies-, and serovar-specific determinants . The genus, or group antigen(s), are lipopolysaccharides similar to those found in gram-negative bacteria and a glycolipid that is secreted by infected cell cultures . Species-specific antigens differentiate Chlamydia trachomatis from Chlamydia psittaci and are expressed on the outer membrane . These proteins range in molecular weight from 155,000 to approximately 40,000 . Monoclonal antibodies to outer-membrane proteins have demonstrated the presence of subspecies-reactive antigenic determinants . Type-specific antigens are associated with the major outer-membrane protein and are secreted from infected cells as well . The molecular weights of these proteins range from 30,000 to 40,000 . These antigens may participate in the binding of the organism to target cells and in an enzymatic process of some type that initiates endocytosis . The significance of the soluble antigens detected in the microenvironment in vitro may suggest immune-complex formation, a process that could contribute to the immunopathology of the disease.

Infect Immun, 1985 Nov, 50(2), 437 - 41
Myelopoiesis in experimentally contaminated specific-pathogen-free and germfree mice during oral administration of polymyxin; Goris H et al.; Oral administration of polymyxin to specific-pathogen-free C3H/Law mice which with previously contaminated with gram-negative bacteria resulted in complete suppression of cecal gram-negative bacteria . Suppression of cecal gram-negative bacteria was accompanied by reduction of the cecal endotoxin concentration from 10 to 1 microgram/g of cecal content as measured with a microtechnique for the Limulus amebocyte lysate assay . Endotoxin determination by this assay appeared to be unaffected by the amount of polymyxin present in cecal preparations after oral administration of this antibiotic . In experimentally contaminated specific-pathogen-free mice, the femoral concentration of progenitor cells forming granulocyte-macrophage colonies in vitro (CFU-GM) decreased significantly (P less than 0.001) to 66% of the initial control after 4 days of polymyxin treatment . However, the femoral CFU-GM concentration in germfree mice and splenic CFU-GM concentration in experimentally contaminated specific-pathogen-free and germfree mice was not affected by polymyxin treatment . The kinetic behavior of femoral and splenic CFU-GM in experimentally contaminated specific-pathogen-free and germfree mice was expressed as the in vivo sensitivity to the S-phase-specific cytostatic drug hydroxyurea, i.e., the hydroxyurea kill . Administration of polymyxin to experimentally contaminated specific-pathogen-free mice significantly diminished the hydroxyurea kill of femoral CFU-GM from 29 to 13% (P less than 0.02) and of splenic CFU-GM from 53 to 27% (P less than 0.005) . The hydroxyurea kill of femoral CFU-GM in germfree mice was not significantly affected by polymyxin treatment . On basis of these results we conclude that the effect of polymyxin treatment on myelopoiesis is most likely due to elimination of intestinal gram-negative bacteria and may indicate a significant role of intestinal gram-negative bacteria in the regulation of myelopoiesis.

Rev Infect Dis, 1985 Nov-Dec, 7 Suppl 4, S648 - 55
Safety profile of aztreonam in clinical trials; Newman TJ et al.; The clinical safety of aztreonam in the treatment of suspected aerobic gram-negative infections was assessed in 346 patients who received single doses and in 2,388 patients who received multiple doses . Of those administered multiple doses, 163 (6.8%) experienced 172 adverse clinical effects . The most common were local reactions at the injection site, rash, diarrhea, and nausea and/or vomiting . Among aztreonam and control groups, three-fold increases in serum aspartate aminotransferase (SGOT) and serum alanine aminotransferase (SGPT) values occurred at comparably low frequencies; the mean values of SGOT and SGPT were slightly higher in patients administered aztreonam than in those given cefamandole . Treatment with aztreonam was discontinued in 51 (2.1%) of 2,388 patients because of adverse clinical effects or abnormal laboratory test values . Suprainfections (infections due to new pathogens occurring at the original site of infection during treatment with the study drug that were treated with another antibiotic) were reported in 2%-6% of aztreonam-treated patients, a frequency similar to that observed in control groups . Aztreonam is well tolerated and has a safety profile similar to that of other beta-lactam antibiotics.

Schweiz Med Wochenschr, 1985 Oct 19, 115(42), 1461 - 5
{Acute abdomen with irreversible shock, a rare but typical complication of hemochromatosis}; Zala G; Acute abdomen, irreversible shock and sudden death are a typical although infrequent complication in patients with hemochromatosis . The author presents a further case of this syndrome and discusses the two leading pathogenetic interpretations described in the literature: sudden release of ferritin, and endotoxin shock . Clinical and post-mortem findings from this patient and a review of 19 cases from the literature suggest that most patients with this syndrome die from a primary bacterial peritonitis with gram negative sepsis and endotoxin shock.

Minerva Med, 1985 Oct 13, 76(39), 1795 - 801
{Cefoperazone: microbiological, kinetic and clinical studies}; Di Nola F et al.; In vitro cefoperazone proved more active against the tested gram-negative bacteria than either piperacillin or mezlocillin . When administered in 1 g venous bolus the antibiotic achieved high plasmatic concentrations that were still adequate after 8 hours . 33.2% was excreted by the kidneys and a considerable amount by the biliary way . Cefoperazone produced a clinical cure in 35/36 patients (97.22%) . A disulfiram-like effect was noted in 18.18%.

Nippon Geka Gakkai Zasshi, 1985 Oct, 86(10), 1426 - 33
{The clinical and pathologic correlations in acute cholangitis}; Shimada H et al.; The liver histology of acute cholangitis was studied in order to determine whether microscopic changes correspond to clinical status . Patients with acute cholangitis were divided into mild cholangitis (1st group, n = 18) and severe cholangitis (2nd, 3rd and 4th groups) accompanied by hypotension . The 2nd group consisted of 6 surviving patients who underwent liver biopsy during hypotension . The 3rd group consisted of 3 non-surviving patients with biopsy during hypotension . The 4th group consisted of 7 patients with biopsy during autopsy . The frequency of endotoxemia, gram negative bacteremia, disseminated intravascular coagulopathy and hepatic failure were significantly higher in severe cholangitis than in mild cholangitis . The incidence of neutrophilic infiltration in the sinusoid and microabscess in lobule were significantly higher in severe cholangitis than in mild one . The incidence of portal thrombosis and massive necrosis of hepatic cells were also significantly higher in severe cholangitis, especially in the 3rd and 4th groups . It was suggested that the neutrophilic infiltration in the sinusoid and microabscess in lobules which proved the existence of endotoxemia or bacteremia were characteristic findings in severe cholangitis.

Fundam Appl Toxicol, 1985 Oct, 5(5), 933 - 47
Aminoglycoside-induced biphasic hindlimb paralysis in the rat: a histological and electrophysiological assessment; Tolliver JM et al.; The intrathecal injection of gentamicin into a human patient with gram-negative bacterial meningitis as well as its intracisternal injection into rabbits caused spongy-like lesions in the gray matter and tetraplegia in rabbits . To characterize this neurotoxic effect, gentamicin was injected into the subarachnoid space of the lumbar spinal cord of the rat . A biphasic hindlimb paralysis ensued which consisted at first of a transient flaccid paralysis lasting 1 to 5 hr followed by a permanent flaccid paralysis which developed after 24 to 36 hr . The initial paralysis occurred simultaneously with the transient loss of reflex transmission through the cord but in the absence of lesions in the spinal cord or physiological alterations of neuromuscular transmission and muscle contraction . The onset of the second phase of paralysis occurred concomitant with changes in reflex transmission and appearance of lesions . Loss of neuromuscular transmission and appearance of signs of denervation (e.g., depolarization, alteration in action potential parameters, and chemosensitivity) appeared after the second phase of paralysis was established . Both the initial transient and late permanent paralysis originated in the spinal cord . The early transient paralysis appears to be due to a central block of transmission while the late paralysis apparently resulted from neuronal damage . The neurotoxic effects of aminoglycosides on neuronal elements in the spinal cord resulted in secondary effects (signs of denervation) in hindlimb muscles.

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